Skip to main content

Activation Approaches on Delivery of Imaging and Therapeutic Agents

  • Chapter
  • First Online:
Engineering in Translational Medicine

Abstract

Successful treatment for a disease relies upon the effective delivery of a therapeutic agent to the target site. An approach to enhance the therapeutic efficacy and to minimize unwanted side effects is to formulate a drug carrier for active and passive targeting. Alternatively, activatable agents have been designed to release active pharmaceutical moieties in response to internal (pH and enzyme) or external (heat, light, and magnetic field) stimuli. Often, the drug releases from these agents are self-regulatory or are remotely controlled in a spatial and/or temporal manner. A site-specific drug release can also improve the therapeutic efficacy, decrease the side effect, and reduce dosage regimen. Complementary to nanotechnology, activatable agents with various built-in sophisticated mechanisms have recently been engineered. Some of them have been used for the development of contrast agents to reduce the imaging background. This chapter provides an update review of activatable agents, with specific examples being highlighted to illustrate their mechanisms and potential applications for imaging and the treatment for diseases, such as cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mittal S, Tsume Y, Landowski CP, Lee KD, Hilfinger JM, Amidon GL (2007) Proline prodrug of melphalan, prophalan-L, demonstrates high therapeutic index in a murine melanoma model. Eur J Pharm Biopharm 67(3):752–758

    Google Scholar 

  2. Garsky VM, Lumma PK, Feng DM, Wai J, Ramjit HG, Sardana MK, Oliff A, Jones RE et al (2001) The synthesis of a prodrug of doxorubicin designed to provide reduced systemic toxicity and greater target efficacy. J Med Chem 44(24):4216–4224

    Google Scholar 

  3. Ryan Q, Ibrahim A, Cohen MH, Johnson J, C-W Ko, Sridhara R, Justice R, Pazdur R (2008) FDA drug approval summary: lapatinib in combination with capecitabine for previously treated metastatic breast cancer that overexpresses HER-2. Oncologist 13(10):1114–1119

    Google Scholar 

  4. Koukourakis GV, Kouloulias V, Koukourakis MJ, Zacharias GA, Zabatis H, Kouvaris J (2008) Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules 13(8):1897–1922

    Google Scholar 

  5. Casak SJ, Lemery SJ, Shen YL, Rothmann MD, Khandelwal A, Zhao H, Davis G, Jarral V et al (2011) US food and drug administration approval: rituximab in combination with fludarabine and cyclophosphamide for the treatment of patients with chronic lymphocytic leukemia. Oncologist 16(1):97–104

    Google Scholar 

  6. Blagosklonny MV (2004) Analysis of FDA approved anticancer drugs reveals the future of cancer therapy. Cell Cycle 3(8):1033–1040

    Google Scholar 

  7. Chow TH, Lin YY, Hwang JJ, Wang HE, Tseng YL, Wang SJ, Liu RS, Lin WJ et al (2009) Improvement of biodistribution and therapeutic index via increase of polyethylene glycol on drug-carrying liposomes in an HT-29/luc xenografted mouse model. Anticancer Res 29(6):2111–2120

    Google Scholar 

  8. Alexis F, Basto P, Levy-Nissenbaum E, Radovic-Moreno AF, Zhang L, Pridgen E, Wang AZ, Marein SL et al (2008) HER-2-targeted nanoparticle–affibody bioconjugates for cancer therapy. Chem Med Chem 3(12):1839–1843

    Google Scholar 

  9. Lim HJ, Masin D, McIntosh NL, Madden TD, Bally MB (2000) Role of drug release and liposome-mediated drug delivery in governing the therapeutic activity of liposomal mitoxantrone used to treat human A431 and LS180 solid tumors. J Pharmacol Exp Ther 292(1):337–345

    Google Scholar 

  10. Lim HJ, Masin D, Madden TD, Bally MB (1997) Influence of drug release characteristics on the therapeutic activity of liposomal mitoxantrone. J Pharmacol Exp Ther 281(1):566–573

    Google Scholar 

  11. Charrois G, Allen TM (2004) Drug release rate influences the pharmacokinetics, biodistribution, therapeutic activity, and toxicity of pegylated liposomal doxorubicin formulations in murine breast cancer. Biochim Biophys Acta 1663(1–2):167

    Google Scholar 

  12. Andresen TL, Jensen SS, Kaasgaard T, Jorgensen K (2005) Triggered activation and release of liposomal prodrugs and drugs in cancer tissue by secretory phospholipase A2. Curr Drug Deliv 2(4):353–362

    Google Scholar 

  13. Huan M, Zhang B, Teng Z, Cui H, Wang J, Liu X, Xia H, Zhou S et al (2012) In vitro and in vivo antitumor activity of a novel pH-activated polymeric drug delivery system for doxorubicin. PLoS One 7(9):e44116

    Google Scholar 

  14. Lu J, Choi E, Tamanoi F, Zink JI (2008) Light-activated nanoimpeller-controlled drug release in cancer cells. Small 4(4):421–426

    Google Scholar 

  15. Griset AP, Walpole J, Liu R, Gaffey A, Colson YL, Grinstaff MW (2009) Expansile nanoparticles: synthesis, characterization, and in vivo efficacy of an acid-responsive polymeric drug delivery system. J Am Chem Soc 131(7):2469–2471

    Google Scholar 

  16. Obata Y, Tajima S, Takeoka S (2010) Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo. J Control Release 142(2):267–276

    Google Scholar 

  17. Morgan TT, Muddana HS, Altinoĝlu EI, Rouse SM, Tabaković A, Tabouillot T, Russin TJ, Shanmugavelandy SS et al (2008) Encapsulation of organic molecules in calcium phosphate nanocomposite particles for intracellular imaging and drug delivery. Nano Lett 8(12):4108–4115

    Google Scholar 

  18. Satarkar NS, Hilt JZ (2008) Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release. J Control Release 130(3):246–251

    Google Scholar 

  19. She W, Li N, Luo K, Guo C, Wang G, Geng Y, Gu Z (2013) Dendronized heparin–doxorubicin conjugate based nanoparticle as pH-responsive drug delivery system for cancer therapy. Biomaterials

    Google Scholar 

  20. Spratt T, Bondurant B, O'Brien DF (2003) Rapid release of liposomal contents upon photoinitiated destabilization with UV exposure. Biochim Biophys Acta 1611(1):35–43

    Google Scholar 

  21. Chen KJ, Liang HF, Chen HL, Wang Y, Cheng PY, Liu HL, Xia Y, Sung HW (2012) A thermoresponsive bubble-generating liposomal system for triggering localized extracellular drug delivery. ACS Nano 7(1):438–446

    Google Scholar 

  22. Huang IP, Sun SP, Cheng SH, Lee CH, Wu CY, Yang CS, Lo LW, Lai YK (2011) Enhanced chemotherapy of cancer using pH-sensitive mesoporous silica nanoparticles to antagonize P-glycoprotein-mediated drug resistance. Mol Cancer Ther 10(5):761–769

    Google Scholar 

  23. Gang J, Park SB, Hyung W, Choi EH, Wen J, Kim HS, Shul YG, Haam S et al (2007) Magnetic poly ϵ-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model. J Drug Target 15(6):445–453

    Google Scholar 

  24. Leite EA, Souza CM, Carvalho-Júnior ÁD, Coelho LG, Lana ÂM, Cassali GD, Oliveira MC (2012) Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity. Int J Nanomedicine 7:5259

    Google Scholar 

  25. Lee JH, Chen KJ, Noh SH, Garcia MA, Wang H, Lin WY, Jeong H, Kong BJ et al (2013) On‐demand drug release system for in vivo cancer treatment through self‐assembled magnetic nanoparticles. Angewandte Chemie International Edition

    Google Scholar 

  26. DeBerardinis RJ, Sayed N, Ditsworth D, Thompson CB (2008) Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev 18(1):54–61

    Google Scholar 

  27. Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141(1):52–67

    Google Scholar 

  28. Cantero D, Friess H, Deflorin J, Zimmermann A, Bründler M, Riesle E, Korc M, Büchler M (1997) Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma. Br J Cancer 75(3):388–395

    Google Scholar 

  29. Berdowska I (2004) Cysteine proteases as disease markers. Clin Chim Acta 342(1–2):41–69

    Google Scholar 

  30. Du JZ, Du XJ, Mao CQ, Wang J (2011) Tailor-made dual pH-sensitive polymer–doxorubicin nanoparticles for efficient anticancer drug delivery. J Am Chem Soc 133(44):17560–17563

    Google Scholar 

  31. Garripelli VK, Kim JK, Son S, Kim WJ, Repka MA, Jo S (2011) Matrix metalloproteinase-sensitive thermogelling polymer for bioresponsive local drug delivery. Acta Biomater 7(5):1984–1992

    Google Scholar 

  32. Lee S, Saito K, Lee HR, Lee MJ, Shibasaki Y, Oishi Y, Kim BS (2012) Hyperbranched double hydrophilic block copolymer micelles of poly (ethylene oxide) and polyglycerol for pH-responsive drug delivery. Biomacromolecules 13(4):1190–1196

    Google Scholar 

  33. Li G, Fei G, Xia H, Han J, Zhao Y (2012) Spatial and temporal control of shape memory polymers and simultaneous drug release using high intensity focused ultrasound. J Mater Chem 22(16):7692–7696

    Google Scholar 

  34. Braun GB, Pallaoro A, Wu G, Missirlis D, Zasadzinski JA, Tirrell M, Reich NO (2009) Laser-activated gene silencing via gold nanoshell–siRNA conjugates. ACS Nano 3(7):2007–2015

    Google Scholar 

  35. Huang X, Lee S, Chen X (2011) Design of “smart” probes for optical imaging of apoptosis. Am J Nucl Med Mol Imaging 1(1):3–17

    Google Scholar 

  36. Ogawa M, Regino CA, Choyke PL, Kobayashi H (2009) In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies. Mol Cancer Ther 8(1):232–239

    Google Scholar 

  37. Ogawa M, Kosaka N, Longmire MR, Urano Y, Choyke PL, Kobayashi H (2009) Fluorophore–quencher based activatable targeted optical probes for detecting in vivo cancer metastases. Mol Pharm 6(2):386–395

    Google Scholar 

  38. Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49(23):6449–6465

    Google Scholar 

  39. Gatenby RA, Gillies RJ (2008) A microenvironmental model of carcinogenesis. Nat Rev Cancer 8(1):56–61

    Google Scholar 

  40. Hashim AI, Zhang X, Wojtkowiak JW, Martinez GV, Gillies RJ (2011) Imaging pH and metastasis. NMR Biomed 24(6):582–591

    Google Scholar 

  41. Cesen MH, Pegan K, Spes A, Turk B (2012) Lysosomal pathways to cell death and their therapeutic applications. Exp Cell Res 318(11):1245–1251

    Google Scholar 

  42. Rodrigues PC, Beyer U, Schumacher P, Roth T, Fiebig HH, Unger C, Messori L, Orioli P et al (1999) Acid-sensitive polyethylene glycol conjugates of doxorubicin: preparation, in vitro efficacy and intracellular distribution. Bioorg Med Chem 7(11):2517–2524

    Google Scholar 

  43. MacKay JA, Chen M, McDaniel JR, Liu W, Simnick AJ, Chilkoti A (2009) Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection. Nat Mater 8(12):993–999

    Google Scholar 

  44. Park HS, Lee JE, Cho MY, Hong JH, Cho SH, Lim YT (2012) Hyaluronic acid/poly(beta-amino ester) polymer nanogels for cancer-cell-specific NIR fluorescence switch. Macromol Rapid Commun 33(18):1549–1555

    Google Scholar 

  45. Murthy N, Thng YX, Schuck S, Xu MC, Frechet JM (2002) A novel strategy for encapsulation and release of proteins: hydrogels and microgels with acid-labile acetal cross-linkers. J Am Chem Soc 124(42):12398–12399

    Google Scholar 

  46. Indira Chandran V, Matesic L, Locke JM, Skropeta D, Ranson M, Vine KL (2012) Anti-cancer activity of an acid-labile N-alkylisatin conjugate targeting the transferrin receptor. Cancer Lett 316(2):151–156

    Google Scholar 

  47. Barth BM, Sharma R, Altinoglu EI, Morgan TT, Shanmugavelandy SS, Kaiser JM, McGovern C, Matters GL et al (2010) Bioconjugation of calcium phosphosilicate composite nanoparticles for selective targeting of human breast and pancreatic cancers in vivo. ACS Nano 4(3):1279–1287

    Google Scholar 

  48. Braslawsky GR, Edson MA, Pearce W, Kaneko T, Greenfield RS (1990) Antitumor activity of adriamycin (hydrazone-linked) immunoconjugates compared with free adriamycin and specificity of tumor cell killing. Cancer Res 50(20):6608–6614

    Google Scholar 

  49. Colombo PE, Boustta M, Poujol S, Jarlier M, Bressolle F, Teulon I, Ladjemi MZ, Pinguet F et al (2011) Intraperitoneal administration of novel doxorubicin loaded polymeric delivery systems against peritoneal carcinomatosis: experimental study in a murine model of ovarian cancer. Gynecol Oncol 122(3):632–640

    Google Scholar 

  50. Chen X, Parelkar SS, Henchey E, Schneider S, Emrick T (2012) PolyMPC-Doxorubicin prodrugs. Bioconjug Chem 23(9):1753–1763

    Google Scholar 

  51. Lin CH, Cheng SH, Liao WN, Wei PR, Sung PJ, Weng CF, Lee CH (2012) Mesoporous silica nanoparticles for the improved anticancer efficacy of cis-platin. Int J Pharm 429(1–2):138–147

    Google Scholar 

  52. Kiziltepe T, Ashley JD, Stefanick JF, Qi YM, Alves NJ, Handlogten MW, Suckow MA, Navari RM et al (2012) Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo. Blood Cancer J 2(4):1–10

    Google Scholar 

  53. Moktan S, Perkins E, Kratz F, Raucher D (2012) Thermal targeting of an acid-sensitive doxorubicin conjugate of elastin-like polypeptide enhances the therapeutic efficacy compared to the parent compound in vivo. Mol Cancer Ther 11(7):1547–1556

    Google Scholar 

  54. Orban E, Mezo G, Schlage P, Csik G, Kulic Z, Ansorge P, Fellinger E, Moller HM et al (2011) In vitro degradation and antitumor activity of oxime bond-linked daunorubicin-GnRH-III bioconjugates and DNA-binding properties of daunorubicin-amino acid metabolites. Amino Acids 41(2):469–483

    Google Scholar 

  55. Szabo I, Manea M, Orban E, Csampai A, Bosze S, Szabo R, Tejeda M, Gaal D et al (2009) Development of an oxime bond containing daunorubicin-gonadotropin-releasing hormone-III conjugate as a potential anticancer drug. Bioconjug Chem 20(4):656–665

    Google Scholar 

  56. Carmona S, Jorgensen MR, Kolli S, Crowther C, Salazar FH, Marion PL, Fujino M, Natori Y et al (2009) Controlling HBV replication in vivo by intravenous administration of triggered PEGylated siRNA-nanoparticles. Mol Pharm 6(3):706–717

    Google Scholar 

  57. Jin Y, Song L, Su Y, Zhu L, Pang Y, Qiu F, Tong G, Yan D et al (2011) Oxime linkage: a robust tool for the design of pH-sensitive polymeric drug carriers. Biomacromolecules 12(10):3460–3468

    Google Scholar 

  58. Kalia J, Raines RT (2008) Hydrolytic stability of hydrazones and oximes. Angew Chem Int Ed Engl 47(39):7523–7526

    Google Scholar 

  59. Oishi M, Nagasaki Y, Itaka K, Nishiyama N, Kataoka K (2005) Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile beta-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells. J Am Chem Soc 127(6):1624–1625

    Google Scholar 

  60. Jeong JH, Kim SW, Park TG (2003) Novel intracellular delivery system of antisense oligonucleotide by self-assembled hybrid micelles composed of DNA/PEG conjugate and cationic fusogenic peptide. Bioconjug Chem 14(2):473–479

    Google Scholar 

  61. Ali MM, Oishi M, Nagatsugi F, Mori K, Nagasaki Y, Kataoka K, Sasaki S (2006) Intracellular inducible alkylation system that exhibits antisense effects with greater potency and selectivity than the natural oligonucleotide. Angew Chem Int Ed Engl 45(19):3136–3140

    Google Scholar 

  62. Oishi M, Nagatsugi F, Sasaki S, Nagasaki Y, Kataoka K (2005) Smart polyion complex micelles for targeted intracellular delivery of PEGylated antisense oligonucleotides containing acid-labile linkages. Chem Bio Chem 6(4):718–725

    Google Scholar 

  63. Vicent MJ, Tomlinson R, Brocchini S, Duncan R (2004) Polyacetal-diethylstilboestrol: a polymeric drug designed for pH-triggered activation. J Drug Target 12(8):491–501

    Google Scholar 

  64. Tomlinson R, Heller J, Brocchini S, Duncan R (2003) Polyacetal-doxorubicin conjugates designed for pH-dependent degradation. Bioconjug Chem 14(6):1096–1106

    Google Scholar 

  65. Su J, Chen F, Cryns VL, Messersmith PB (2011) Catechol polymers for pH-responsive, targeted drug delivery to cancer cells. J Am Chem Soc 133(31):11850–11853

    Google Scholar 

  66. Cr K, Thapa B, Xu P (2012) pH and redox dual responsive nanoparticle for nuclear targeted drug delivery. Mol Pharm 9(9):2719–2729

    Google Scholar 

  67. Bae Y, Alani AW, Rockich NC, Lai TS, Kwon GS (2010) Mixed pH-sensitive polymeric micelles for combination drug delivery. Pharm Res 27(11):2421–2432

    Google Scholar 

  68. Zhu S, Lansakara PD, Li X, Cui Z (2012) Lysosomal delivery of a lipophilic gemcitabine prodrug using novel acid-sensitive micelles improved its antitumor activity. Bioconjug Chem 23(5):966–980

    Google Scholar 

  69. Wang B, Xu C, Xie J, Yang Z, Sun S (2008) pH controlled release of chromone from chromone-Fe3O4 nanoparticles. J Am Chem Soc 130(44):14436–14437

    Google Scholar 

  70. Xu S, Luo Y, Graeser R, Warnecke A, Kratz F, Hauff P, Licha K, Haag R (2009) Development of pH-responsive core-shell nanocarriers for delivery of therapeutic and diagnostic agents. Bioorg Med Chem Lett 19(3):1030–1034

    Google Scholar 

  71. Griset AP, Walpole J, Liu R, Gaffey A, Colson YL, Grinstaff MW (2009) Expansile nanoparticles: synthesis, characterization, and in vivo efficacy of an acid-responsive polymeric drug delivery system. J Am Chem Soc 131(7):2469–2471

    Google Scholar 

  72. Xu Z, Gu W, Chen L, Gao Y, Zhang Z, Li Y (2008) A smart nanoassembly consisting of acid-labile vinyl ether PEG-DOPE and protamine for gene delivery: preparation and in vitro transfection. Biomacromolecules 9(11):3119–3126

    Google Scholar 

  73. Koren E, Apte A, Jani A, Torchilin VP (2012) Multifunctional PEGylated 2C5-immunoliposomes containing pH-sensitive bonds and TAT peptide for enhanced tumor cell internalization and cytotoxicity. J Control Release 160(2):264–273

    Google Scholar 

  74. Lee ES, Na K, Bae YH (2003) Polymeric micelle for tumor pH and folate-mediated targeting. J Control Release 91(1–2):103–113

    Google Scholar 

  75. Lee ES, Na K, Bae YH (2005) Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7 tumor. J Control Release 103(2):405–418

    Google Scholar 

  76. Song W, Tang Z, Li M, Lv S, Yu H, Ma L, Zhuang X, Huang Y et al (2012) Tunable pH-sensitive poly(beta-amino ester)s synthesized from primary amines and diacrylates for intracellular drug delivery. Macromol Biosci 12(10):1375–1383

    Google Scholar 

  77. Kim JH, Li Y, Kim MS, Kang SW, Jeong JH, Lee DS (2012) Synthesis and evaluation of biotin-conjugated pH-responsive polymeric micelles as drug carriers. Int J Pharm 427(2):435–442

    Google Scholar 

  78. Shen Y, Tang H, Zhan Y, Van Kirk EA, Murdoch WJ (2009) Degradable poly(beta-amino ester) nanoparticles for cancer cytoplasmic drug delivery. Nanomedicine 5(2):192–201

    Google Scholar 

  79. Koo H, Lee H, Lee S, Min KH, Kim MS, Lee DS, Choi Y, Kwon IC et al (2010) In vivo tumor diagnosis and photodynamic therapy via tumoral pH-responsive polymeric micelles. Chem Commun (Camb) 46(31):5668–5670

    Google Scholar 

  80. Gao GH, Lee JW, Nguyen MK, Im GH, Yang J, Heo H, Jeon P, Park TG et al (2011) pH-responsive polymeric micelle based on PEG-poly(beta-amino ester)/(amido amine) as intelligent vehicle for magnetic resonance imaging in detection of cerebral ischemic area. J Control Release 155(1):11–17

    Google Scholar 

  81. Kim D, Lee ES, Park K, Kwon IC, Bae YH (2008) Doxorubicin loaded pH-sensitive micelle: antitumoral efficacy against ovarian A2780/DOXR tumor. Pharm Res 25(9):2074–2082

    Google Scholar 

  82. Kondo S, Yamamoto K, Sawama Y, Sasai Y, Yamauchi Y, Kuzuya M (2011) Characterization of novel pH-sensitive polymeric micelles prepared by the self-assembly of amphiphilic block copolymer with poly-4-vinylpyridine block synthesized by mechanochemical solid-state polymerization. Chem Pharm Bull (Tokyo) 59(9):1200–1202

    Google Scholar 

  83. Kester M, Heakal Y, Fox T, Sharma A, Robertson GP, Morgan TT, Altinoglu EI, Tabakovic A et al (2008) Calcium phosphate nanocomposite particles for in vitro imaging and encapsulated chemotherapeutic drug delivery to cancer cells. Nano Lett 8(12):4116–4121

    Google Scholar 

  84. Barroug A, Glimcher MJ (2002) Hydroxyapatite crystals as a local delivery system for cisplatin: adsorption and release of cisplatin in vitro. J Orthop Res 20(2):274–280

    Google Scholar 

  85. Min KH, Lee HJ, Kim K, Kwon IC, Jeong SY, Lee SC (2012) The tumor accumulation and therapeutic efficacy of doxorubicin carried in calcium phosphate-reinforced polymer nanoparticles. Biomaterials 33(23):5788–5797

    Google Scholar 

  86. Muhammad F, Guo M, Qi W, Sun F, Wang A, Guo Y, Zhu G (2011) pH-triggered controlled drug release from mesoporous silica nanoparticles via intracellular dissolution of ZnO nanolids. J Am Chem Soc 133(23):8778–8781

    Google Scholar 

  87. Fiallo MM, Garnier-Suillerot A, Matzanke B, Kozlowski H (1999) How Fe3+ binds anthracycline antitumour compounds. The myth and the reality of a chemical sphinx. J Inorg Biochem 75(2):105–115

    Google Scholar 

  88. Chen Y, Wan Y, Wang Y, Zhang H, Jiao Z (2011) Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles. Int J Nanomedicine 6:2321–2326

    Google Scholar 

  89. Chen Y, Chen H, Zhang S, Chen F, Sun S, He Q, Ma M, Wang X et al (2012) Structure-property relationships in manganese oxide–mesoporous silica nanoparticles used for T1-weighted MRI and simultaneous anti-cancer drug delivery. Biomaterials 33(7):2388–2398

    Google Scholar 

  90. Shin J, Anisur RM, Ko MK, Im GH, Lee JH, Lee IS (2009) Hollow manganese oxide nanoparticles as multifunctional agents for magnetic resonance imaging and drug delivery. Angew Chem Int Ed Engl 48(2):321–324

    Google Scholar 

  91. Zhang H, Wang C, Chen B, Wang X (2012) Daunorubicin-TiO2 nanocomposites as a “smart” pH-responsive drug delivery system. Int J Nanomedicine 7:235–242

    Google Scholar 

  92. Muhammad F, Guo M, Guo Y, Qi W, Qu F, Sun F, Zhao H, Zhu G (2011) Acid degradable ZnO quantum dots as a platform for targeted delivery of an anticancer drug. J Mater Chem 21(35):13406–13412

    Google Scholar 

  93. Na HB, Lee JH, An K, Park YI, Park M, Lee IS, Nam DH, Kim ST et al (2007) Development of a T1 contrast agent for magnetic resonance imaging using MnO nanoparticles. Angew Chem Int Ed Engl 46(28):5397–5401

    Google Scholar 

  94. Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS (2012) Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy. Int J Nanomedicine 7:4077–4088

    Google Scholar 

  95. Zhang H, Mardyani S, Chan WC, Kumacheva E (2006) Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics. Biomacromolecules 7(5):1568–1572

    Google Scholar 

  96. Zhou T, Xiao C, Fan J, Chen S, Shen J, Wu W, Zhou S (2012) A nanogel of on-site tunable pH-response for efficient anticancer drug delivery. Acta Biomater 9(1):4546–4557

    Google Scholar 

  97. Wu W, Shen J, Banerjee P, Zhou S (2010) Chitosan-based responsive hybrid nanogels for integration of optical pH-sensing, tumor cell imaging and controlled drug delivery. Biomaterials 31(32):8371–8381

    Google Scholar 

  98. Duan C, Zhang D, Wang F, Zheng D, Jia L, Feng F, Liu Y, Wang Y et al (2011) Chitosan-g-poly(N-isopropylacrylamide) based nanogels for tumor extracellular targeting. Int J Pharm 409(1):252–259

    Google Scholar 

  99. Andresen TL, Thompson DH, Kaasgaard T (2010) Enzyme-triggered nanomedicine: drug release strategies in cancer therapy. Mol Membr Biol 27(7):353–363

    Google Scholar 

  100. Law B, Tung CH (2009) Proteolysis: a biological process adapted in drug delivery, therapy, and imaging. Bioconjug Chem 20(9):1683–1695

    Google Scholar 

  101. Puente XS, Sanchez LM, Gutierrez-Fernandez A, Velasco G, Lopez-Otin C (2005) A genomic view of the complexity of mammalian proteolytic systems. Biochem Soc Trans 33(Pt 2):331–334

    Google Scholar 

  102. Silk DB (1980) Digestion and absorption of dietary protein in man. Proc Nutr Soc 39(1):61–70

    Google Scholar 

  103. Nilsson IM (1987) Coagulation and fibrinolysis. Scand J Gastroenterol Suppl 137:11–18

    Google Scholar 

  104. Tong W, Zhang L (2012) Fetal hypoxia and programming of matrix metalloproteinases. Drug Discov Today 17(3–4):124–134

    MathSciNet  Google Scholar 

  105. Hyman BT, Yuan J (2012) Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology. Nat Rev Neurosci 13(6):395–406

    Google Scholar 

  106. Cipollone F, Prontera C, Pini B, Marini M, Fazia M, De Cesare D, Iezzi A, Ucchino S et al (2001) Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability. Circulation 104(8):921–927

    Google Scholar 

  107. Loftus IM, Naylor AR, Goodall S, Crowther M, Jones L, Bell PR, Thompson MM (2000) Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption. Stroke 31(1):40–47

    Google Scholar 

  108. Papalambros E, Sigala F, Georgopoulos S, Panou N, Kavatzas N, Agapitos M, Bastounis E (2004) Vascular endothelial growth factor and matrix metalloproteinase 9 expression in human carotid atherosclerotic plaques: relationship with plaque destabilization via neovascularization. Cerebrovasc Dis 18(2):160–165

    Google Scholar 

  109. Baruah DB, Dash RN, Chaudhari MR, Kadam SS (2006) Plasminogen activators: a comparison. Vascul Pharmacol 44(1):1–9

    Google Scholar 

  110. Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11:529–543

    Google Scholar 

  111. Gueders MM, Foidart JM, Noel A, Cataldo DD (2006) Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: potential implications in asthma and other lung diseases. Eur J Pharmacol 533(1–3):133–144

    Google Scholar 

  112. Churg A, Wright JL (2005) Proteases and emphysema. Curr Opin Pulm Med 11(2):153–159

    Google Scholar 

  113. Deaton DN, Tavares FX (2005) Design of cathepsin K inhibitors for osteoporosis. Curr Top Med Chem 5(16):1639–1675

    Google Scholar 

  114. Kobayashi H, Schmitt M, Goretzki L, Chucholowski N, Calvete J, Kramer M, Gunzler WA, Janicke F et al (1991) Cathepsin B efficiently activates the soluble and the tumor cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (Pro-uPA). J Biol Chem 266(8):5147–5152

    Google Scholar 

  115. Nabeshima K, Inoue T, Shimao Y, Sameshima T (2002) Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int 52(4):255–264

    Google Scholar 

  116. Blasi F, Carmeliet P (2002) uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 3(12):932–943

    Google Scholar 

  117. Lee M, Fridman R, Mobashery S (2004) Extracellular proteases as targets for treatment of cancer metastases. Chem Soc Rev 33(7):401–409

    Google Scholar 

  118. Koblinski JE, Ahram M, Sloane BF (2000) Unraveling the role of proteases in cancer. Clin Chim Acta 291(2):113–135

    Google Scholar 

  119. Maly DJ, Huang L, Ellman JA (2002) Combinatorial strategies for targeting protein families: application to the proteases. Chem Bio Chem 3(1):16–37

    Google Scholar 

  120. Aureli L, Gioia M, Cerbara I, Monaco S, Fasciglione GF, Marini S, Ascenzi P, Topai A et al (2008) Structural bases for substrate and inhibitor recognition by matrix metalloproteinases. Curr Med Chem 15(22):2192–2222

    Google Scholar 

  121. Carl PL, Chakravarty PK, Katzenellenbogen JA, Weber MJ (1980) Protease-activated “prodrugs” for cancer chemotherapy. Proc Natl Acad Sci USA 77(4):2224–2228

    Google Scholar 

  122. Chakravarty PK, Carl PL, Weber MJ, Katzenellenbogen JA (1983) Plasmin-activated prodrugs for cancer chemotherapy. 1. Synthesis and biological activity of peptidylacivicin and peptidylphenylenediamine mustard. J Med Chem 26(5):633–638

    Google Scholar 

  123. Balajthy Z, Aradi J, Kiss IT, Elodi P (1992) Synthesis and functional evaluation of a peptide derivative of 1-beta-D-arabinofuranosylcytosine. J Med Chem 35(18):3344–3349

    Google Scholar 

  124. Albright CF, Graciani N, Han W, Yue E, Stein R, Lai Z, Diamond M, Dowling R et al (2005) Matrix metalloproteinase-activated doxorubicin prodrugs inhibit HT1080 xenograft growth better than doxorubicin with less toxicity. Mol Cancer Ther 4(5):751–760

    Google Scholar 

  125. Timar F, Botyanszki J, Suli-Vargha H, Babo I, Olah J, Pogany G, Jeney A (1998) The antiproliferative action of a melphalan hexapeptide with collagenase-cleavable site. Cancer Chemother Pharmacol 41(4):292–298

    Google Scholar 

  126. Kline T, Torgov MY, Mendelsohn BA, Cerveny CG, Senter PD (2004) Novel antitumor prodrugs designed for activation by matrix metalloproteinases-2 and -9. Mol Pharm 1(1):9–22

    Google Scholar 

  127. DeFeo-Jones D, Brady SF, Feng DM, Wong BK, Bolyar T, Haskell K, Kiefer DM, Leander K et al (2002) A prostate-specific antigen (PSA)-activated vinblastine prodrug selectively kills PSA-secreting cells in vivo. Mol Cancer Ther 1(7):451–459

    Google Scholar 

  128. Denmeade SR, Nagy A, Gao J, Lilja H, Schally AV, Isaacs JT (1998) Enzymatic activation of a doxorubicin-peptide prodrug by prostate-specific antigen. Cancer Res 58(12):2537–2540

    Google Scholar 

  129. DeFeo-Jones D, Garsky VM, Wong BK, Feng DM, Bolyar T, Haskell K, Kiefer DM, Leander K et al (2000) A peptide-doxorubicin ‘prodrug' activated by prostate-specific antigen selectively kills prostate tumor cells positive for prostate-specific antigen in vivo. Nat Med 6(11):1248–1252

    Google Scholar 

  130. DiPaola RS, Rinehart J, Nemunaitis J, Ebbinghaus S, Rubin E, Capanna T, Ciardella M, Doyle-Lindrud S et al (2002) Characterization of a novel prostate-specific antigen-activated peptide-doxorubicin conjugate in patients with prostate cancer. J Clin Oncol 20(7):1874–1879

    Google Scholar 

  131. Szeto HH, Lovelace JL, Fridland G, Soong Y, Fasolo J, Wu D, Desiderio DM, Schiller PW (2001) In vivo pharmacokinetics of selective mu-opioid peptide agonists. J Pharmacol Exp Ther 298(1):57–61

    Google Scholar 

  132. Doronina SO, Toki BE, Torgov MY, Mendelsohn BA, Cerveny CG, Chace DF, DeBlanc RL, Gearing RP et al (2003) Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 21(7):778–784

    Google Scholar 

  133. Gualberto A (2012) Brentuximab Vedotin (SGN-35), an antibody-drug conjugate for the treatment of CD30-positive malignancies. Expert Opin Investig Drugs 21(2):205–216

    Google Scholar 

  134. Gianolio DA, Rouleau C, Bauta WE, Lovett D, Cantrell WR Jr, Recio A 3rd, Wolstenholme-Hogg P, Busch M et al (2012) Targeting HER2-positive cancer with dolastatin 15 derivatives conjugated to trastuzumab, novel antibody-drug conjugates. Cancer Chemother Pharmacol 70(3):439–449

    Google Scholar 

  135. Elsadek B, Graeser R, Esser N, Schafer-Obodozie C, Abu Ajaj K, Unger C, Warnecke A, Saleem T et al (2010) Development of a novel prodrug of paclitaxel that is cleaved by prostate-specific antigen: an in vitro and in vivo evaluation study. Eur J Cancer 46(18):3434–3444

    Google Scholar 

  136. Palandoken H, By K, Hegde M, Harley WR, Gorin FA, Nantz MH (2005) Amiloride peptide conjugates: prodrugs for sodium-proton exchange inhibition. J Pharmacol Exp Ther 312(3):961–967

    Google Scholar 

  137. Kumar SK, Roy I, Anchoori RK, Fazli S, Maitra A, Beachy PA, Khan SR (2008) Targeted inhibition of hedgehog signaling by cyclopamine prodrugs for advanced prostate cancer. Bioorg Med Chem 16(6):2764–2768

    Google Scholar 

  138. Jiang Y, Dipaola RS, Hu L (2009) Synthesis and stereochemical preference of peptide 4-aminocyclophosphamide conjugates as potential prodrugs of phosphoramide mustard for activation by prostate-specific antigen (PSA). Bioorg Med Chem Lett 19(9):2587–2590

    Google Scholar 

  139. Dubois V, Nieder M, Collot F, Negrouk A, Nguyen TT, Gangwar S, Reitz B, Wattiez R et al (2006) Thimet oligopeptidase (EC 3.4.24.15) activates CPI-0004Na, an extracellularly tumour-activated prodrug of doxorubicin. Eur J Cancer 42(17):3049–3056

    Google Scholar 

  140. Shi NQ, Gao W, Xiang B, Qi XR (2012) Enhancing cellular uptake of activable cell-penetrating peptide-doxorubicin conjugate by enzymatic cleavage. Int J Nanomedicine 7:1613–1621

    Google Scholar 

  141. Lim SH, Jeong YI, Moon KS, Ryu HH, Jin YH, Jin SG, Jung TY, Kim IY et al (2010) Anticancer activity of PEGylated matrix metalloproteinase cleavable peptide-conjugated adriamycin against malignant glioma cells. Int J Pharm 387(1–2):209–214

    Google Scholar 

  142. de Groot FM, Broxterman HJ, Adams HP, van Vliet A, Tesser GI, Elderkamp YW, Schraa AJ, Kok RJ et al (2002) Design, synthesis, and biological evaluation of a dual tumor-specific motive containing integrin-targeted plasmin-cleavable doxorubicin prodrug. Mol Cancer Ther 1(11):901–911

    Google Scholar 

  143. de Groot FM, de Bart AC, Verheijen JH, Scheeren HW (1999) Synthesis and biological evaluation of novel prodrugs of anthracyclines for selective activation by the tumor-associated protease plasmin. J Med Chem 42(25):5277–5283

    Google Scholar 

  144. Graeser R, Chung DE, Esser N, Moor S, Schachtele C, Unger C, Kratz F (2008) Synthesis and biological evaluation of an albumin-binding prodrug of doxorubicin that is cleaved by prostate-specific antigen (PSA) in a PSA-positive orthotopic prostate carcinoma model (LNCaP). Int J Cancer 122(5):1145–1154

    Google Scholar 

  145. Liu C, Sun C, Huang H, Janda K, Edgington T (2003) Overexpression of legumain in tumors is significant for invasion/metastasis and a candidate enzymatic target for prodrug therapy. Cancer Res 63(11):2957–2964

    Google Scholar 

  146. Mhaka A, Denmeade SR, Yao W, Isaacs JT, Khan SR (2002) A 5-fluorodeoxyuridine prodrug as targeted therapy for prostate cancer. Bioorg Med Chem Lett 12(17):2459–2461

    Google Scholar 

  147. Tanihara M, Suzuki Y, Nishimura Y, Suzuki K, Kakimaru Y, Fukunishi Y (1999) A novel microbial infection-responsive drug release system. J Pharm Sci 88(5):510–514

    Google Scholar 

  148. Fiehn C, Kratz F, Sass G, Muller-Ladner U, Neumann E (2008) Targeted drug delivery by in vivo coupling to endogenous albumin: an albumin-binding prodrug of methotrexate (MTX) is better than MTX in the treatment of murine collagen-induced arthritis. Ann Rheum Dis 67(8):1188–1191

    Google Scholar 

  149. de Groot FM, Loos WJ, Koekkoek R, van Berkom LW, Busscher GF, Seelen AE, Albrecht C, de Bruijn P et al (2001) Elongated multiple electronic cascade and cyclization spacer systems in activatible anticancer prodrugs for enhanced drug release. J Org Chem 66(26):8815–8830

    Google Scholar 

  150. Liang L, Lin SW, Dai W, Lu JK, Yang TY, Xiang Y, Zhang Y, Li RT et al (2012) Novel cathepsin B-sensitive paclitaxel conjugate: Higher water solubility, better efficacy and lower toxicity. J Control Release 160(3):618–629

    Google Scholar 

  151. Yamada R, Kostova MB, Anchoori RK, Xu S, Neamati N, Khan SR (2010) Biological evaluation of paclitaxel-peptide conjugates as a model for MMP2-targeted drug delivery. Cancer Biol Ther 9(3):192–203

    Google Scholar 

  152. Lo PC, Chen J, Stefflova K, Warren MS, Navab R, Bandarchi B, Mullins S, Tsao M et al (2009) Photodynamic molecular beacon triggered by fibroblast activation protein on cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers. J Med Chem 52(2):358–368

    Google Scholar 

  153. Chen J, Stefflova K, Niedre MJ, Wilson BC, Chance B, Glickson JD, Zheng G (2004) Protease-triggered photosensitizing beacon based on singlet oxygen quenching and activation. J Am Chem Soc 126(37):11450–11451

    Google Scholar 

  154. Tai W, Shukla RS, Qin B, Li B, Cheng K (2011) Development of a peptide-drug conjugate for prostate cancer therapy. Mol Pharm 8(3):901–912

    Google Scholar 

  155. Denmeade SR, Jakobsen CM, Janssen S, Khan SR, Garrett ES, Lilja H, Christensen SB, Isaacs JT (2003) Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer. J Natl Cancer Inst 95(13):990–1000

    Google Scholar 

  156. Janssen S, Jakobsen CM, Rosen DM, Ricklis RM, Reineke U, Christensen SB, Lilja H, Denmeade SR (2004) Screening a combinatorial peptide library to develop a human glandular kallikrein 2-activated prodrug as targeted therapy for prostate cancer. Mol Cancer Ther 3(11):1439–1450

    Google Scholar 

  157. Pan H, Kopeckova P, Wang D, Yang J, Miller S, Kopecek J (2006) Water-soluble HPMA copolymer–prostaglandin E1 conjugates containing a cathepsin K sensitive spacer. J Drug Target 14(6):425–435

    Google Scholar 

  158. Pan H, Liu J, Dong Y, Sima M, Kopeckova P, Brandi ML, Kopecek J (2008) Release of prostaglandin E(1) from N-(2-hydroxypropyl)methacrylamide copolymer conjugates by bone cells. Macromol Biosci 8(7):599–605

    Google Scholar 

  159. Putnam D, Kopecek J (1995) Enantioselective release of 5-fluorouracil from N-(2-hydroxypropyl)methacrylamide-based copolymers via lysosomal enzymes. Bioconjug Chem 6(4):483–492

    Google Scholar 

  160. Seymour LW, Ferry DR, Kerr DJ, Rea D, Whitlock M, Poyner R, Boivin C, Hesslewood S et al (2009) Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer. Int J Oncol 34(6):1629–1636

    Google Scholar 

  161. Etrych T, Kovar L, Strohalm J, Chytil P, Rihova B, Ulbrich K (2011) Biodegradable star HPMA polymer-drug conjugates: Biodegradability, distribution and anti-tumor efficacy. J Control Release 154(3):241–248

    Google Scholar 

  162. Duncan R, Kopeckova P, Strohalm J, Hume IC, Lloyd JB, Kopecek J (1988) Anticancer agents coupled to N-(2-hydroxypropyl)methacrylamide copolymers. II. Evaluation of daunomycin conjugates in vivo against L1210 leukaemia. Br J Cancer 57(2):147–156

    Google Scholar 

  163. Gianasi E, Buckley RG, Latigo J, Wasil M, Duncan R (2002) HPMA copolymers platinates containing dicarboxylato ligands. Preparation, characterisation and in vitro and in vivo evaluation. J Drug Target 10(7):549–556

    Google Scholar 

  164. Satchi-Fainaro R, Puder M, Davies JW, Tran HT, Sampson DA, Greene AK, Corfas G, Folkman J (2004) Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470. Nat Med 10(3):255–261

    Google Scholar 

  165. Potrich C, Tomazzolli R, Dalla Serra M, Anderluh G, Malovrh P, Macek P, Menestrina G, Tejuca M (2005) Cytotoxic activity of a tumor protease-activated pore-forming toxin. Bioconjug Chem 16(2):369–376

    Google Scholar 

  166. Schmid B, Chung DE, Warnecke A, Fichtner I, Kratz F (2007) Albumin-binding prodrugs of camptothecin and doxorubicin with an Ala-Leu-Ala-Leu-linker that are cleaved by cathepsin B: synthesis and antitumor efficacy. Bioconjug Chem 18(3):702–716

    Google Scholar 

  167. Abu Ajaj K, Graeser R, Fichtner I, Kratz F (2009) In vitro and in vivo study of an albumin-binding prodrug of doxorubicin that is cleaved by cathepsin B. Cancer Chemother Pharmacol 64(2):413–418

    Google Scholar 

  168. Mansour AM, Drevs J, Esser N, Hamada FM, Badary OA, Unger C, Fichtner I, Kratz F (2003) A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Cancer Res 63(14):4062–4066

    Google Scholar 

  169. Kratz F, Drevs J, Bing G, Stockmar C, Scheuermann K, Lazar P, Unger C (2001) Development and in vitro efficacy of novel MMP2 and MMP9 specific doxorubicin albumin conjugates. Bioorg Med Chem Lett 11(15):2001–2006

    Google Scholar 

  170. Chung DE, Kratz F (2006) Development of a novel albumin-binding prodrug that is cleaved by urokinase-type-plasminogen activator (uPA). Bioorg Med Chem Lett 16(19):5157–5163

    Google Scholar 

  171. Shiose Y, Ochi Y, Kuga H, Yamashita F, Hashida M (2007) Relationship between drug release of DE-310, macromolecular prodrug of DX-8951f, and cathepsins activity in several tumors. Biol Pharm Bull 30(12):2365–2370

    Google Scholar 

  172. Chau Y, Dang NM, Tan FE, Langer R (2006) Investigation of targeting mechanism of new dextran-peptide-methotrexate conjugates using biodistribution study in matrix-metalloproteinase-overexpressing tumor xenograft model. J Pharm Sci 95(3):542–551

    Google Scholar 

  173. Chandran SS, Nan A, Rosen DM, Ghandehari H, Denmeade SR (2007) A prostate-specific antigen activated N-(2-hydroxypropyl) methacrylamide copolymer prodrug as dual-targeted therapy for prostate cancer. Mol Cancer Ther 6(11):2928–2937

    Google Scholar 

  174. Chipman SD, Oldham FB, Pezzoni G, Singer JW (2006) Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. Int J Nanomedicine 1(4):375–383

    Google Scholar 

  175. Dan AG, Saha S, Monson KM, Wiese D, Schochet E, Barber KR, Ganatra B, Desai D et al (2004) 1 % lymphazurin vs 10 % fluorescein for sentinel node mapping in colorectal tumors. Arch Surg 139(11):1180–1184

    Google Scholar 

  176. Detter C, Russ D, Iffland A, Wipper S, Schurr MO, Reichenspurner H, Buess G, Reichart B (2002) Near-infrared fluorescence coronary angiography: a new noninvasive technology for intraoperative graft patency control. Heart Surg Forum 5(4):364–369

    Google Scholar 

  177. Lane PM, Lam S, McWilliams A, Leriche JC, Anderson MW, Macaulay CE (2009) Confocal fluorescence microendoscopy of bronchial epithelium. J Biomed Opt 14(2):024008

    Google Scholar 

  178. Albayrak Y, Oren D, Gundogdu C, Kurt A (2011) Intraoperative sentinel lymph node mapping in patients with colon cancer: study of 38 cases. Turk J Gastroenterol 22(3):286–292

    Google Scholar 

  179. Varghese P, Abdel-Rahman AT, Akberali S, Mostafa A, Gattuso JM, Carpenter R (2008) Methylene blue dye–a safe and effective alternative for sentinel lymph node localization. Breast J 14(1):61–67

    Google Scholar 

  180. Goetz M, Toermer T, Vieth M, Dunbar K, Hoffman A, Galle PR, Neurath MF, Delaney P et al (2009) Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet. Gastrointest Endosc 70(5):959–968

    Google Scholar 

  181. Xa Zhang, Lovejoy KS, Jasanoff A, Lippard SJ (2007) Water-soluble porphyrins as a dual-function molecular imaging platform for MRI and fluorescence zinc sensing. Proc Natl Acad Sci USA 104(26):10780–10785

    Google Scholar 

  182. Law B, Curino A, Bugge TH, Weissleder R, Tung CH (2004) Design, synthesis, and characterization of urokinase plasminogen-activator-sensitive near-infrared reporter. Chem Biol 11(1):99–106

    Google Scholar 

  183. Hsiao JK, Law B, Weissleder R, Tung CH (2006) In-vivo imaging of tumor associated urokinase-type plasminogen activator activity. J Biomed Opt 11(3):34013

    Google Scholar 

  184. Tung CH, Mahmood U, Bredow S, Weissleder R (2000) In vivo imaging of proteolytic enzyme activity using a novel molecular reporter. Cancer Res 60(17):4953–4958

    Google Scholar 

  185. Abd-Elgaliel WR, Cruz-Monserrate Z, Logsdon CD, Tung CH (2011) Molecular imaging of cathepsin E-positive tumors in mice using a novel protease-activatable fluorescent probe. Mol BioSyst 7(12):3207–3213

    Google Scholar 

  186. Jaffer FA, Kim DE, Quinti L, Tung CH, Aikawa E, Pande AN, Kohler RH, Shi GP et al (2007) Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease-activatable fluorescence sensor. Circulation 115(17):2292–2298

    Google Scholar 

  187. Bremer C, Bredow S, Mahmood U, Weissleder R, Tung CH (2001) Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model. Radiology 221(2):523–529

    Google Scholar 

  188. Bremer C, Tung CH, Weissleder R (2001) In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat Med 7(6):743–748

    Google Scholar 

  189. Messerli SM, Prabhakar S, Tang Y, Shah K, Cortes ML, Murthy V, Weissleder R, Breakefield XO et al (2004) A novel method for imaging apoptosis using a caspase-1 near-infrared fluorescent probe. Neoplasia 6(2):95–105

    Google Scholar 

  190. Lu Z, Yeh TK, Tsai M, Au JL, Wientjes MG (2004) Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy. Clin Cancer Res 10(22):7677–7684

    Google Scholar 

  191. Biswas A, Liu Y, Liu T, Fan G, Tang Y (2012) Polyethylene glycol-based protein nanocapsules for functional delivery of a differentiation transcription factor. Biomaterials 33(21):5459–5467

    Google Scholar 

  192. Clark MR, Aliyar HA, Lee CW, Jay JI, Gupta KM, Watson KM, Stewart RJ, Buckheit RW et al (2011) Enzymatic triggered release of an HIV-1 entry inhibitor from prostate specific antigen degradable microparticles. Int J Pharm 413(1–2):10–18

    Google Scholar 

  193. Fukami T, Yokoi T (2012) The emerging role of human esterases. Drug Metab Pharmacokinet 27(5):466–477

    Google Scholar 

  194. Montagnani F, Chiriatti A, Licitra S, Aliberti C, Fiorentini G (2010) Differences in efficacy and safety between capecitabine and infusional 5-fluorouracil when combined with irinotecan for the treatment of metastatic colorectal cancer. Clin Colorectal Cancer 9(4):243–247

    Google Scholar 

  195. Tang M, Mukundan M, Yang J, Charpentier N, LeCluyse EL, Black C, Yang D, Shi D et al (2006) Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol. J Pharmacol Exp Ther 319(3):1467–1476

    Google Scholar 

  196. Shi D, Yang J, Yang D, LeCluyse EL, Black C, You L, Akhlaghi F, Yan B (2006) Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther 319(3):1477–1484

    Google Scholar 

  197. Zhang J, Burnell JC, Dumaual N, Bosron WF (1999) Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1. J Pharmacol Exp Ther 290(1):314–318

    Google Scholar 

  198. Sun Z, Murry DJ, Sanghani SP, Davis WI, Kedishvili NY, Zou Q, Hurley TD, Bosron WF (2004) Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther 310(2):469–476

    Google Scholar 

  199. Howard MD, Lu X, Rinehart JJ, Jay M, Dziubla TD (2012) Carboxylesterase-triggered hydrolysis of nanoparticle PEGylating agents. Langmuir 28(33):12030–12037

    Google Scholar 

  200. Agostini A, Mondragon L, Pascual L, Aznar E, Coll C, Martinez-Manez R, Sancenon F, Soto J et al (2012) Design of enzyme-mediated controlled release systems based on silica mesoporous supports capped with ester-glycol groups. Langmuir 28(41):14766–14776

    Google Scholar 

  201. Azagarsamy MA, Sokkalingam P, Thayumanavan S (2009) Enzyme-triggered disassembly of dendrimer-based amphiphilic nanocontainers. J Am Chem Soc 131(40):14184–14185

    Google Scholar 

  202. Green PS, Mendez AJ, Jacob JS, Crowley JR, Growdon W, Hyman BT, Heinecke JW (2004) Neuronal expression of myeloperoxidase is increased in Alzheimer's disease. J Neurochem 90(3):724–733

    Google Scholar 

  203. Zhang R, Brennan ML, Fu X, Aviles RJ, Pearce GL, Penn MS, Topol EJ, Sprecher DL et al (2001) Association between myeloperoxidase levels and risk of coronary artery disease. JAMA 286(17):2136–2142

    Google Scholar 

  204. Choi DK, Pennathur S, Perier C, Tieu K, Teismann P, Wu DC, Jackson-Lewis V, Vila M et al (2005) Ablation of the inflammatory enzyme myeloperoxidase mitigates features of Parkinson's disease in mice. J Neurosci 25(28):6594–6600

    Google Scholar 

  205. Re G, Azzimondi G, Lanzarini C, Bassein L, Vaona I, Guarnieri C (1997) Plasma lipoperoxidative markers in ischaemic stroke suggest brain embolism. Eur J Emerg Med 4(1):5–9

    Google Scholar 

  206. Ishida-Okawara A, Oharaseki T, Takahashi K, Hashimoto Y, Aratani Y, Koyama H, Maeda N, Naoe S et al (2001) Contribution of myeloperoxidase to coronary artery vasculitis associated with MPO-ANCA production. Inflammation 25(6):381–387

    Google Scholar 

  207. Chen JW, Pham W, Weissleder R, Bogdanov A Jr (2004) Human myeloperoxidase: a potential target for molecular MR imaging in atherosclerosis. Magn Reson Med 52(5):1021–1028

    Google Scholar 

  208. Nahrendorf M, Sosnovik D, Chen JW, Panizzi P, Figueiredo JL, Aikawa E, Libby P, Swirski FK et al (2008) Activatable magnetic resonance imaging agent reports myeloperoxidase activity in healing infarcts and noninvasively detects the antiinflammatory effects of atorvastatin on ischemia-reperfusion injury. Circulation 117(9):1153–1160

    Google Scholar 

  209. Querol M, Chen JW, Weissleder R, Bogdanov A Jr (2005) DTPA-bisamide-based MR sensor agents for peroxidase imaging. Org Lett 7(9):1719–1722

    Google Scholar 

  210. Rodriguez E, Nilges M, Weissleder R, Chen JW (2010) Activatable magnetic resonance imaging agents for myeloperoxidase sensing: mechanism of activation, stability, and toxicity. J Am Chem Soc 132(1):168–177

    Google Scholar 

  211. Breckwoldt MO, Chen JW, Stangenberg L, Aikawa E, Rodriguez E, Qiu S, Moskowitz MA, Weissleder R (2008) Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci USA 105(47):18584–18589

    Google Scholar 

  212. Ronald JA, Chen JW, Chen Y, Hamilton AM, Rodriguez E, Reynolds F, Hegele RA, Rogers KA et al (2009) Enzyme-sensitive magnetic resonance imaging targeting myeloperoxidase identifies active inflammation in experimental rabbit atherosclerotic plaques. Circulation 120(7):592–599

    Google Scholar 

  213. Chen JW, Querol Sans M, Bogdanov A Jr, Weissleder R (2006) Imaging of myeloperoxidase in mice by using novel amplifiable paramagnetic substrates. Radiology 240(2):473–481

    Google Scholar 

  214. Kim JH, Lee S, Park K, Nam HY, Jang SY, Youn I, Kim K, Jeon H et al (2007) Protein-phosphorylation-responsive polymeric nanoparticles for imaging protein kinase activities in single living cells. Angew Chem Int Ed Engl 46(30):5779–5782

    Google Scholar 

  215. Oishi J, Kawamura K, Kang JH, Kodama K, Sonoda T, Murata M, Niidome T, Katayama Y (2006) An intracellular kinase signal-responsive gene carrier for disordered cell-specific gene therapy. J Control Release 110(2):431–436

    Google Scholar 

  216. Fernandes A, Viterisi A, Coutrot F, Potok S, Leigh DA, Aucagne V, Papot S (2009) Rotaxane-based propeptides: protection and enzymatic release of a bioactive pentapeptide. Angew Chem Int Ed Engl 48(35):6443–6447

    Google Scholar 

  217. Kamal A, Tekumalla V, Krishnan A, Pal-Bhadra M, Bhadra U (2008) Development of pyrrolo[2,1-c][1, 4]benzodiazepine beta-galactoside prodrugs for selective therapy of cancer by ADEPT and PMT. Chem Med Chem 3(5):794–802

    Google Scholar 

  218. Thomas M, Rivault F, Tranoy-Opalinski I, Roche J, Gesson JP, Papot S (2007) Synthesis and biological evaluation of the suberoylanilide hydroxamic acid (SAHA) beta-glucuronide and beta-galactoside for application in selective prodrug chemotherapy. Bioorg Med Chem Lett 17(4):983–986

    Google Scholar 

  219. Fang L, Battisti RF, Cheng H, Reigan P, Xin Y, Shen J, Ross D, Chan KK et al (2006) Enzyme specific activation of benzoquinone ansamycin prodrugs using HuCC49DeltaCH2-beta-galactosidase conjugates. J Med Chem 49(21):6290–6297

    Google Scholar 

  220. Yu Y, Fang L, Sun D (2010) Biodistribution of HuCC49DeltaCH2-beta-galactosidase in colorectal cancer xenograft model. Int J Pharm 386(1–2):208–215

    Google Scholar 

  221. Ho NH, Weissleder R, Tung CH (2007) A self-immolative reporter for beta-galactosidase sensing. Chem Bio Chem 8(5):560–566

    Google Scholar 

  222. Valdagni R, Amichetti M (1994) Report of long-term follow-up in a randomized trial comparing radiation therapy and radiation therapy plus hyperthermia to metastatic lymph nodes in stage IV head and neck patients. Int J Radiat Oncol Biol Phys 28(1):163–169

    Google Scholar 

  223. Vernon CC, Hand JW, Field SB, Machin D, Whaley JB, van der Zee J, van Putten WL, van Rhoon GC et al (1996) Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group. Int J Radiat Oncol Biol Phys 35(4):731–744

    Google Scholar 

  224. Sneed PK, Stauffer PR, McDermott MW, Diederich CJ, Lamborn KR, Prados MD, Chang S, Weaver KA et al (1998) Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost ± hyperthermia for glioblastoma multiforme. Int J Radiat Oncol Biol Phys 40(2):287–295

    Google Scholar 

  225. Hamazoe R, Maeta M, Kaibara N (1994) Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of gastric cancer. Final results of a randomized controlled study. Cancer 73(8):2048–2052

    Google Scholar 

  226. Kawai N, Ito A, Nakahara Y, Futakuchi M, Shirai T, Honda H, Kobayashi T, Kohri K (2005) Anticancer effect of hyperthermia on prostate cancer mediated by magnetite cationic liposomes and immune-response induction in transplanted syngeneic rats. Prostate 64(4):373–381

    Google Scholar 

  227. Okano T, Yamada N, Sakai H, Sakurai Y (1993) A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly(N-isopropylacrylamide). J Biomed Mater Res 27(10):1243–1251

    Google Scholar 

  228. Okano T, Yamada N, Okuhara M, Sakai H, Sakurai Y (1995) Mechanism of cell detachment from temperature-modulated, hydrophilic-hydrophobic polymer surfaces. Biomaterials 16(4):297–303

    Google Scholar 

  229. Yang M, Ding Y, Zhang L, Qian X, Jiang X, Liu B (2007) Novel thermosensitive polymeric micelles for docetaxel delivery. J Biomed Mater Res A 81(4):847–857

    Google Scholar 

  230. Liu B, Yang M, Li X, Qian X, Shen Z, Ding Y, Yu L (2008) Enhanced efficiency of thermally targeted taxanes delivery in a human xenograft model of gastric cancer. J Pharm Sci 97(8):3170–3181

    Google Scholar 

  231. Park JS, Akiyama Y, Yamasaki Y, Kataoka K (2007) Preparation and characterization of polyion complex micelles with a novel thermosensitive poly(2-isopropyl-2-oxazoline) shell via the complexation of oppositely charged block ionomers. Langmuir 23(1):138–146

    Google Scholar 

  232. Toti US, Moon SH, Kim HY, Jun YJ, Kim BM, Park YM, Jeong B, Sohn YS (2007) Thermosensitive and biocompatible cyclotriphosphazene micelles. J Control Release 119(1):34–40

    Google Scholar 

  233. Bae KH, Choi SH, Park SY, Lee Y, Park TG (2006) Thermosensitive pluronic micelles stabilized by shell cross-linking with gold nanoparticles. Langmuir 22(14):6380–6384

    Google Scholar 

  234. Chung JE, Yokoyama M, Yamato M, Aoyagi T, Sakurai Y, Okano T (1999) Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate). J Control Release 62(1–2):115–127

    Google Scholar 

  235. Zhu JL, Zhang XZ, Cheng H, Li YY, Cheng SX, Zhuo RX (2007) Synthesis and characterization of well-defined, Amphiphilic Poly(N-isopropylacrylamide)-b-[2-hydroxyethyl methacrylate-poly(epsilon-caprolactone)](n) graft copolymers by RAFT polymerization and macromonomer method. J Polym Sci [A1] 45(22):5354–5364

    Google Scholar 

  236. Wei H, Chen WQ, Chang C, Cheng C, Cheng SX, Zhang XZ, Zhuo RX (2008) Synthesis of star block, thermosensitive poly(L-lactide)-star block-poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide) copolymers and their self-assembled micelles for controlled release. J Phys Chem 112(8):2888–2894

    Google Scholar 

  237. Nakayama M, Okano T, Miyazaki T, Kohori F, Sakai K, Yokoyama M (2006) Molecular design of biodegradable polymeric micelles for temperature-responsive drug release. J Control Release 115(1):46–56

    Google Scholar 

  238. Liu SQ, Tong YW, Yang YY (2005) Incorporation and in vitro release of doxorubicin in thermally sensitive micelles made from poly(N-isopropylacrylamide-co-N, N-dimethylacrylamide)-b-poly(D, L-lactide-co-glycolide) with varying compositions. Biomaterials 26(24):5064–5074

    Google Scholar 

  239. Na K, Lee KH, Lee DH, Bae YH (2006) Biodegradable thermo-sensitive nanoparticles from poly(L-lactic acid)/poly(ethylene glycol) alternating multi-block copolymer for potential anti-cancer drug carrier. Eur J Pharm Sci 27(2–3):115–122

    Google Scholar 

  240. Yatvin MB, Weinstein JN, Dennis WH, Blumenthal R (1978) Design of liposomes for enhanced local release of drugs by hyperthermia. Science 202(4374):1290–1293

    Google Scholar 

  241. Needham D, Anyarambhatla G, Kong G, Dewhirst MW (2000) A new temperature-sensitive liposome for use with mild hyperthermia: characterization and testing in a human tumor xenograft model. Cancer Res 60(5):1197–1201

    Google Scholar 

  242. Chen Q, Tong S, Dewhirst MW, Yuan F (2004) Targeting tumor microvessels using doxorubicin encapsulated in a novel thermosensitive liposome. Mol Cancer Ther 3(10):1311–1317

    Google Scholar 

  243. Chang HI, Yeh MK (2012) Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy. Int J Nanomedicine 7:49–60

    Google Scholar 

  244. Kong G, Anyarambhatla G, Petros WP, Braun RD, Colvin OM, Needham D, Dewhirst MW (2000) Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res 60(24):6950–6957

    Google Scholar 

  245. Al-Ahmady ZS, Al-Jamal WT, Bossche JV, Bui TT, Drake AF, Mason AJ, Kostarelos K (2012) Lipid-Peptide vesicle nanoscale hybrids for triggered drug release by mild hyperthermia in vitro and in vivo. ACS Nano 6(10):9335–9346

    Google Scholar 

  246. Tong X, Wang G, Soldera A, Zhao Y (2005) How can azobenzene block copolymer vesicles be dissociated and reformed by light? J Phys Chem B 109(43):20281–20287

    Google Scholar 

  247. Fomina N, McFearin C, Sermsakdi M, Edigin O, Almutairi A (2010) UV and near-IR triggered release from polymeric nanoparticles. J Am Chem Soc 132(28):9540–9542

    Google Scholar 

  248. Cabane E, Malinova V, Meier W (2010) Synthesis of photocleavable amphiphilic block copolymers: toward the design of photosensitive nanocarriers. Macromol Chem Phys 211(17):1847–1856

    Google Scholar 

  249. Lv C, Wang Z, Wang P, Tang X (2012) Photodegradable polyurethane self-assembled nanoparticles for photocontrollable release. Langmuir 28(25):9387–9394

    Google Scholar 

  250. Babin J, Pelletier M, Lepage M, Allard JF, Morris D, Zhao Y (2009) A new two-photon-sensitive block copolymer nanocarrier. Angew Chem Int Ed Engl 48(18):3329–3332

    Google Scholar 

  251. Yan B, Boyer JC, Branda NR, Zhao Y (2011) Near-infrared light-triggered dissociation of block copolymer micelles using upconverting nanoparticles. J Am Chem Soc 133(49):19714–19717

    Google Scholar 

  252. Hribar KC, Lee MH, Lee D, Burdick JA (2011) Enhanced release of small molecules from near-infrared light responsive polymer-nanorod composites. ACS Nano 5(4):2948–2956

    Google Scholar 

  253. Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Rivera B, Price RE, Hazle JD, Halas NJ et al (2003) Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc Natl Acad Sci USA 100(23):13549–13554

    Google Scholar 

  254. Skrabalak SE, Au L, Lu X, Li X, Xia Y (2007) Gold nanocages for cancer detection and treatment. Nanomedicine (Lond) 2(5):657–668

    Google Scholar 

  255. Huang X, El-Sayed IH, Qian W, El-Sayed MA (2006) Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 128(6):2115–2120

    Google Scholar 

  256. Lu W, Xiong C, Zhang G, Huang Q, Zhang R, Zhang JZ, Li C (2009) Targeted photothermal ablation of murine melanomas with melanocyte-stimulating hormone analog-conjugated hollow gold nanospheres. Clin Cancer Res 15(3):876–886

    Google Scholar 

  257. Melancon MP, Lu W, Yang Z, Zhang R, Cheng Z, Elliot AM, Stafford J, Olson T et al (2008) In vitro and in vivo targeting of hollow gold nanoshells directed at epidermal growth factor receptor for photothermal ablation therapy. Mol Cancer Ther 7(6):1730–1739

    Google Scholar 

  258. Zhou M, Zhang R, Huang M, Lu W, Song S, Melancon MP, Tian M, Liang D et al (2010) A chelator-free multifunctional [64Cu]CuS nanoparticle platform for simultaneous micro-PET/CT imaging and photothermal ablation therapy. J Am Chem Soc 132(43):15351–15358

    Google Scholar 

  259. Melancon MP, Zhou M, Li C (2011) Cancer theranostics with near-infrared light-activatable multimodal nanoparticles. Acc Chem Res 44(10):947–956

    Google Scholar 

  260. You J, Zhang R, Zhang G, Zhong M, Liu Y, Van Pelt CS, Liang D, Wei W et al (2012) Photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres: A platform for near-infrared light-trigged drug release. J Control Release 158(2):319–328

    Google Scholar 

  261. Regmi R, Bhattarai SR, Sudakar C, Wani AS, Cunningham R, Vaishnava PP, Naik R, Oupicky D et al (2010) Hyperthermia controlled rapid drug release from thermosensitive magnetic microgels. J Mater Chem 20(29):6158–6163

    Google Scholar 

  262. Katagiri K, Imai Y, Koumoto K (2011) Variable on-demand release function of magnetoresponsive hybrid capsules. J Colloid Interface Sci 361(1):109–114

    Google Scholar 

  263. Liu TY, Hu SH, Liu KH, Shaiu RS, Liu DM, Chen SY (2008) Instantaneous drug delivery of magnetic/thermally sensitive nanospheres by a high-frequency magnetic field. Langmuir 24(23):13306–13311

    Google Scholar 

  264. Liu J, Zhang Y, Wang C, Xu R, Chen Z, Gu N (2010) Magnetically sensitive alginate-templated polyelectrolyte multilayer microcapsules for controlled release of doxorubicin. J Phys Chem C 114(17):7673–7679

    Google Scholar 

  265. Hu SH, Tsai CH, Liao CF, Liu DM, Chen SY (2008) Controlled rupture of magnetic polyelectrolyte microcapsules for drug delivery. Langmuir 24(20):11811–11818

    Google Scholar 

  266. Liu C, Guo J, Yang W, Hu J, Wang C, Fu S (2009) Magnetic mesoporous silica microspheres with thermo-sensitive polymer shell for controlled drug release. J Mater Chem 19(27):4764–4770

    Google Scholar 

  267. Oliveira H, Pérez-Andrés E, Thevenot J, Sandre O, Berra E, Lecommandoux S (2013) Magnetic field triggered drug release from polymersomes for cancer therapeutics. J Control Release

    Google Scholar 

  268. Zhao X, Kim J, Cezar CA, Huebsch N, Lee K, Bouhadir K, Mooney DJ (2011) Active scaffolds for on-demand drug and cell delivery. Proc Natl Acad Sci USA 108(1):67–72

    Google Scholar 

  269. Hu SH, Liu TY, Huang HY, Liu DM, Chen SY (2008) Magnetic-sensitive silica nanospheres for controlled drug release. Langmuir 24(1):239–244

    Google Scholar 

  270. Brazel CS (2009) Magnetothermally-responsive nanomaterials: combining magnetic nanostructures and thermally-sensitive polymers for triggered drug release. Pharm Res 26(3):644–656

    Google Scholar 

  271. Hu SH, Liu TY, Huang HY, Liu DM, Chen SY (2009) Stimuli-responsive controlled drug release from magnetic-sensitive silica nanospheres. J Nanosci Nanotechnol 9(2):866–870

    Google Scholar 

  272. Clares B, Biedma-Ortiz RA, Sáez-Fernández E, Prados JC, Melguizo C, Cabeza L, Ortiz R, Arias JL (2013) Nano-engineering of 5-fluorouracil-loaded magnetoliposomes for combined hyperthermia and chemotherapy against colon cancer. Eur J Pharm Biopharm

    Google Scholar 

  273. Chen Y, Bose A, Bothun GD (2010) Controlled release from bilayer-decorated magnetoliposomes via electromagnetic heating. ACS Nano 4(6):3215–3221

    Google Scholar 

  274. Qiu D, An X (2012) Controllable release from magnetoliposomes by magnetic stimulation and thermal stimulation. Colloids Surf B Biointerfaces 104:326–329

    Google Scholar 

  275. Yoshida M, Sato M, Yamamoto Y, Maehara T, Naohara T, Aono H, Sugishita H, Sato K et al (2012) Tumor local chemohyperthermia using docetaxel-embedded magnetoliposomes: Interaction of chemotherapy and hyperthermia. J Gastroenterol Hepatol 27(2):406–411

    Google Scholar 

  276. Ito A, Fujioka M, Yoshida T, Wakamatsu K, Ito S, Yamashita T, Jimbow K, Honda H (2007) 4-S-Cysteaminylphenol-loaded magnetite cationic liposomes for combination therapy of hyperthermia with chemotherapy against malignant melanoma. Cancer Sci 98(3):424–430

    Google Scholar 

  277. Yoshida M, Watanabe Y, Sato M, Maehara T, Aono H, Naohara T, Hirazawa H, Horiuchi A et al (2010) Feasibility of chemohyperthermia with docetaxel-embedded magnetoliposomes as minimally invasive local treatment for cancer. Int J Cancer 126(8):1955–1965

    Google Scholar 

  278. Hayashi K, Ono K, Suzuki H, Sawada M, Moriya M, Sakamoto W, Yogo T (2010) High-frequency, magnetic-field-responsive drug release from magnetic nanoparticle/organic hybrid based on hyperthermic effect. ACS Appl Mater Interfaces 2(7):1903–1911

    Google Scholar 

  279. Mikhaylov G, Mikac U, Magaeva AA, Itin VI, Naiden EP, Psakhye I, Babes L, Reinheckel T et al (2011) Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. Nat Nanotechnol 6(9):594–602

    Google Scholar 

  280. Ruiz-Hernández E, Baeza A, Ma Vallet-Regí (2011) Smart drug delivery through DNA/magnetic nanoparticle gates. ACS Nano 5(2):1259–1266

    Google Scholar 

  281. Thomas CR, Ferris DP, Lee JH, Choi E, Cho MH, Kim ES, Stoddart JF, Shin JS et al (2010) Noninvasive remote-controlled release of drug molecules in vitro using magnetic actuation of mechanized nanoparticles. J Am Chem Soc 132(31):10623–10625

    Google Scholar 

  282. Wang YC, Wang F, Sun TM, Wang J (2011) Redox-responsive nanoparticles from the single disulfide bond-bridged block copolymer as drug carriers for overcoming multidrug resistance in cancer cells. Bioconjug Chem 22(10):1939–1945

    Google Scholar 

  283. Liu J, Pang Y, Huang W, Zhu Z, Zhu X, Zhou Y, Yan D (2011) Redox-responsive polyphosphate nanosized assemblies: a smart drug delivery platform for cancer therapy. Biomacromolecules 12(6):2407–2415

    Google Scholar 

  284. Zhao M, Biswas A, Hu B, Joo KI, Wang P, Gu Z, Tang Y (2011) Redox-responsive nanocapsules for intracellular protein delivery. Biomaterials 32(22):5223–5230

    Google Scholar 

  285. Kuang Y, Balakrishnan K, Gandhi V, Peng X (2011) Hydrogen peroxide inducible DNA cross-linking agents: targeted anticancer prodrugs. J Am Chem Soc 133(48):19278–19281

    Google Scholar 

  286. Liu J, Pang Y, Zhu Z, Wang D, Li C, Huang W, Zhu X, Yan D (2013) Therapeutic nanocarriers with hydrogen peroxide-triggered drug release for cancer treatment. Biomacromolecules

    Google Scholar 

  287. Ge J, Neofytou E, Cahill TJ III, Beygui RE, Zare RN (2011) Drug release from electric-field-responsive nanoparticles. ACS Nano 6(1):227–233

    Google Scholar 

  288. Zhu Y, Liu H, Li F, Ruan Q, Wang H, Fujiwara M, Wang L, Lu G (2010) Dipolar molecules as impellers achieving electric-field-stimulated release. J Am Chem Soc 132(5):1450–1451

    Google Scholar 

  289. Fantozzi F, Arturoni E, Barbucci R (2010) The effects of the electric fields on hydrogels to achieve antitumoral drug release. Bioelectrochemistry 78(2):191–195

    Google Scholar 

  290. Yudina A, de Smet M, Lepetit-Coiffe M, Langereis S, Van Ruijssevelt L, Smirnov P, Bouchaud V, Voisin P et al (2011) Ultrasound-mediated intracellular drug delivery using microbubbles and temperature-sensitive liposomes. J Control Release 155(3):442–448

    Google Scholar 

  291. Yin T, Wang P, Li J, Zheng R, Zheng B, Cheng D, Li R, Lai J et al. (2013) Ultrasound-sensitive siRNA-loaded nanobubbles formed by hetero-assembly of polymeric micelles and liposomes and their therapeutic effect in gliomas. Biomaterials

    Google Scholar 

  292. Yan F, Li L, Deng Z, Jin Q, Chen J, Yang W, Yeh CK, Wu J et al (2013) Paclitaxel-liposome–microbubble complexes as ultrasound-triggered therapeutic drug delivery carriers. J Control Release 166(3):246–255

    Google Scholar 

  293. Han D, Tong X, Zhao Y (2012) Block copolymer micelles with a dual-stimuli-responsive core for fast or slow degradation. Langmuir 28(5):2327–2331

    Google Scholar 

  294. Li Y, Tong R, Xia H, Zhang H, Xuan J (2010) High intensity focused ultrasound and redox dual responsive polymer micelles. Chem Commun 46(41):7739–7741

    Google Scholar 

  295. Tong R, Xia H, Lu X (2013) Fast release behavior of block copolymer micelles under high intensity focused ultrasound/redox combined stimulus. J Mater Chem 1(6):886–894

    Google Scholar 

  296. Korin N, Kanapathipillai M, Matthews BD, Crescente M, Brill A, Mammoto T, Ghosh K, Jurek S et al (2012) Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science 337(6095):738–742

    Google Scholar 

  297. Matsumoto A, Yamamoto K, Yoshida R, Kataoka K, Aoyagi T, Miyahara Y (2010) A totally synthetic glucose responsive gel operating in physiological aqueous conditions. Chem Commun 46(13):2203–2205

    Google Scholar 

  298. Yao Y, Zhao L, Yang J, Yang J (2012) Glucose-responsive vehicles containing phenylborate ester for controlled insulin release at neutral pH. Biomacromolecules 13(6):1837–1844

    Google Scholar 

  299. Traitel T, Cohen Y, Kost J (2000) Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions. Biomaterials 21(16):1679–1687

    Google Scholar 

  300. Agarwal A, Boettcher A, Kneuer R, Sari-Sarraf F, Donovan A, Woelcke J, Simic O, Brandl T et al (2013) In vivo imaging with fluorescent smart probes to assess treatment strategies for acute pancreatitis. PLoS One 8(2):e55959

    Google Scholar 

  301. Al-Jamal WT, Al-Ahmady ZS, Kostarelos K (2012) Pharmacokinetics and tissue distribution of temperature-sensitive liposomal doxorubicin in tumor-bearing mice triggered with mild hyperthermia. Biomaterials 33(18):4608–4617

    Google Scholar 

  302. Liu TY, Hu SH, Liu DM, Chen SY, Chen IW (2009) Biomedical nanoparticle carriers with combined thermal and magnetic responses. Nano Today 4(1):52–65

    MathSciNet  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Benedict Law .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag London

About this chapter

Cite this chapter

Patel, M.A., Law, B. (2014). Activation Approaches on Delivery of Imaging and Therapeutic Agents. In: Cai, W. (eds) Engineering in Translational Medicine. Springer, London. https://doi.org/10.1007/978-1-4471-4372-7_26

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4372-7_26

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4371-0

  • Online ISBN: 978-1-4471-4372-7

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics