Smart Stimuli-Responsive Nano-sized Hosts for Drug Delivery

  • Majid HosseiniEmail author
  • Fatemeh FarjadianEmail author
  • Abdel Salam Hamdy MakhloufEmail author


The evolution in the synthesis of smart polymers broadens new horizons for their potent application in medicine, especially in drug delivery. Many synthetic polymers that exhibit environmentally responsive behavior are potential smart carrier candidates that allow for controlled therapeutic delivery. These materials can be loaded with specific drugs for therapeutic applications, releasing treatment in response to a stimulus. This stimuli-responsive capability has enabled smart polymeric materials to distribute drugs in response to commonly known exogenous and/or endogenous stimuli. Examples of these various stimuli include pH, enzyme concentration, temperature, ultrasound intensity, as well as light, magnetic field, redox gradients and a multitude of other potential stimuli. This chapter provides a detailed critical discussion and an overview of the stimuli-responsive polymers which have found applications in targeted drug delivery. Furthermore, multiresponsive systems and their forthcoming development as well as challenges associated with some stimuli-responsive systems are discussed. Finally, the most recent and emerging trends along with a look toward expected future breakthroughs using these types of nanocarriers are discussed.


Smart polymers Stimuli-responsive polymers Nanocarriers Drug delivery 



The authors would like to thank Ms. Zahra Bagheri Nezhad from Raykasoft Inc., for her assistant with designing Figs. 1.1 and 1.6.


  1. 1.
    Schwartz M (2008) Smart materials. CRC Press, Boca Raton, FLCrossRefGoogle Scholar
  2. 2.
    Aguilar MR, Roman J (2014) Smart polymers and their applications. Elsevier, CambridgeGoogle Scholar
  3. 3.
    Galaev I, Mattiasson B (2007) Smart polymers: applications in biotechnology and biomedicine. CRC Press, Boca Raton, FLCrossRefGoogle Scholar
  4. 4.
    Hu J, Zhang G, Liu S (2012) Enzyme-responsive polymeric assemblies, nanoparticles and hydrogels. Chem Soc Rev 41(18):5933–5949CrossRefGoogle Scholar
  5. 5.
    Mura S, Nicolas J, Couvreur P (2013) Stimuli-responsive nanocarriers for drug delivery. Nat Mater 12(11):991–1003CrossRefGoogle Scholar
  6. 6.
    Jhaveri AM, Torchilin VP (2014) Multifunctional polymeric micelles for delivery of drugs and siRNA. Front Pharmacol 5:77, 10.3389/fphar.2014.00077CrossRefGoogle Scholar
  7. 7.
    Riess G (2003) Micellization of block copolymers. Prog Polym Sci 28(7):1107–1170CrossRefGoogle Scholar
  8. 8.
    Braunecker WA, Matyjaszewski K (2007) Controlled/living radical polymerization: features, developments, and perspectives. Prog Polym Sci 32(1):93–146CrossRefGoogle Scholar
  9. 9.
    Smith AE, Xu X, McCormick CL (2010) Stimuli-responsive amphiphilic (co) polymers via RAFT polymerization. Prog Polym Sci 35(1):45–93CrossRefGoogle Scholar
  10. 10.
    Yokoyama M (2005) Drug targeting with nano-sized carrier systems. J Artif Organs 8(2):77–84CrossRefGoogle Scholar
  11. 11.
    Miyata K, Christie RJ, Kataoka K (2011) Polymeric micelles for nano-scale drug delivery. React Funct Polym 71(3):227–234CrossRefGoogle Scholar
  12. 12.
    Rodriguez-Hernandez J, Chécot F, Gnanou Y, Lecommandoux S (2005) Toward ‘smart’ nano-objects by self-assembly of block copolymers in solution. Prog Polym Sci 30(7):691–724CrossRefGoogle Scholar
  13. 13.
    Mohamed S, Parayath NN, Taurin S, Greish K (2014) Polymeric nano-micelles: versatile platform for targeted delivery in cancer. Ther Delivery 5(10):1101–1121CrossRefGoogle Scholar
  14. 14.
    Akimoto J, Nakayama M, Okano T (2014) Temperature-responsive polymeric micelles for optimizing drug targeting to solid tumors. J Control Release 193:2–8CrossRefGoogle Scholar
  15. 15.
    Roy D, Brooks WL, Sumerlin BS (2013) New directions in thermoresponsive polymers. Chem Soc Rev 42(17):7214–7243CrossRefGoogle Scholar
  16. 16.
    Strandman S, Zhu X (2015) Thermo-responsive block copolymers with multiple phase transition temperatures in aqueous solutions. Prog Polym Sci 42:154–176CrossRefGoogle Scholar
  17. 17.
    Bernstein R, Cruz C, Paul D, Barlow J (1977) Behavior in polymer blends. Macromolecules 10(3):681–686CrossRefGoogle Scholar
  18. 18.
    Hocine S, Li M-H (2013) Thermoresponsive self-assembled polymer colloids in water. Soft Matter 9(25):5839–5861CrossRefGoogle Scholar
  19. 19.
    Wei H, Cheng S-X, Zhang X-Z, Zhuo R-X (2009) Thermo-sensitive polymeric micelles based on poly (N-isopropylacrylamide) as drug carriers. Prog Polym Sci 34(9):893–910CrossRefGoogle Scholar
  20. 20.
    James HP, John R, Alex A, Anoop K (2014) Smart polymers for the controlled delivery of drugs–a concise overview. Acta Pharm Sin B 4(2):120–127CrossRefGoogle Scholar
  21. 21.
    Xu J, Liu S (2008) Polymeric nanocarriers possessing thermoresponsive coronas. Soft Matter 4(9):1745–1749CrossRefGoogle Scholar
  22. 22.
    Hales M, Barner-Kowollik C, Davis TP, Stenzel MH (2004) Shell-cross-linked vesicles synthesized from block copolymers of poly (D, L-lactide) and poly (N-isopropyl acrylamide) as thermoresponsive nanocontainers. Langmuir 20(25):10809–10817CrossRefGoogle Scholar
  23. 23.
    Cammas S, Suzuki K, Sone C, Sakurai Y, Kataoka K, Okano T (1997) Thermo-responsive polymer nanoparticles with a core-shell micelle structure as site-specific drug carriers. J Control Release 48(2):157–164CrossRefGoogle Scholar
  24. 24.
    Nishiyama N, Kataoka K (2006) Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery. Pharmacol Ther 112(3):630–648CrossRefGoogle Scholar
  25. 25.
    Chung J, 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):115–127CrossRefGoogle Scholar
  26. 26.
    Chung J, Yokoyama M, Suzuki K, Aoyagi T, Sakurai Y, Okano T (1997) Reversibly thermo-responsive alkyl-terminated poly (N-isopropylacrylamide) core-shell micellar structures. Colloids Surf B 9(1):37–48CrossRefGoogle Scholar
  27. 27.
    Chung J, Yokoyama M, Aoyagi T, Sakurai Y, Okano T (1998) Effect of molecular architecture of hydrophobically modified poly (N-isopropylacrylamide) on the formation of thermoresponsive core-shell micellar drug carriers. J Control Release 53(1):119–130CrossRefGoogle Scholar
  28. 28.
    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):46–56CrossRefGoogle Scholar
  29. 29.
    Akimoto J, Nakayama M, Sakai K, Okano T (2010) Thermally controlled intracellular uptake system of polymeric micelles possessing poly (N-isopropylacrylamide)-based outer coronas. Mol Pharm 7(4):926–935CrossRefGoogle Scholar
  30. 30.
    Sun X-L, Tsai P-C, Bhat R, Bonder E, Michniak-Kohn B, Pietrangelo A (2015) Thermoresponsive block copolymer micelles with tunable pyrrolidone-based polymer cores: structure/property correlations and application as drug carriers. J Mater Chem B 3(5):814–823CrossRefGoogle Scholar
  31. 31.
    Liu J, Huang Y, Kumar A, Tan A, Jin S, Mozhi A, Liang X-J (2014) pH-sensitive nano-systems for drug delivery in cancer therapy. Biotechnol Adv 32(4):693–710CrossRefGoogle Scholar
  32. 32.
    Dai S, Ravi P, Tam KC (2008) pH-responsive polymers: synthesis, properties and applications. Soft Matter 4(3):435–449CrossRefGoogle Scholar
  33. 33.
    Liu Y, Wang W, Yang J, Zhou C, Sun J (2013) pH-sensitive polymeric micelles triggered drug release for extracellular and intracellular drug targeting delivery. Asian J Pharm Sci 8(3):159–167CrossRefGoogle Scholar
  34. 34.
    Thomas JL, Barton SW, Tirrell DA (1994) Membrane solubilization by a hydrophobic polyelectrolyte: surface activity and membrane binding. Biophys J 67(3):1101CrossRefGoogle Scholar
  35. 35.
    Mellman I, Fuchs R, Helenius A (1986) Acidification of the endocytic and exocytic pathways. Annu Rev Biochem 55(1):663–700CrossRefGoogle Scholar
  36. 36.
    Iversen T-G, Skotland T, Sandvig K (2011) Endocytosis and intracellular transport of nanoparticles: present knowledge and need for future studies. Nano Today 6(2):176–185CrossRefGoogle Scholar
  37. 37.
    Fattal E, Couvreur P, Dubernet C (2004) “Smart” delivery of antisense oligonucleotides by anionic pH-sensitive liposomes. Adv Drug Deliv Rev 56(7):931–946CrossRefGoogle Scholar
  38. 38.
    Chen T, Mcintosh D, He Y, Kim J, Tirrell DA, Scherrer P, Fenske DB, Sandhu AP, Cullis PR (2004) Alkylated derivatives of poly (ethylacrylic acid) can be inserted into preformed liposomes and trigger pH-dependent intracellular delivery of liposomal contents. Mol Membr Biol 21(6):385–393CrossRefGoogle Scholar
  39. 39.
    Henry SM, El-Sayed ME, Pirie CM, Hoffman AS, Stayton PS (2006) pH-responsive poly (styrene-alt-maleic anhydride) alkylamide copolymers for intracellular drug deliver. Biomacromolecules 7(8):2407–2414CrossRefGoogle Scholar
  40. 40.
    Gaucher G, Satturwar P, Jones M-C, Furtos A, Leroux J-C (2010) Polymeric micelles for oral drug delivery. Eur J Pharm Biopharm 76(2):147–158CrossRefGoogle Scholar
  41. 41.
    Leroux J-C, Cozens RM, Roesel JL, Galli B, Doelker E, Gurny R (1996) pH-sensitive nanoparticles: an effective means to improve the oral delivery of HIV-1 protease inhibitors in dogs. Pharm Res 13(3):485–487CrossRefGoogle Scholar
  42. 42.
    De Jaeghere F, Allémann E, Kubel F, Galli B, Cozens R, Doelker E, Gurny R (2000) Oral bioavailability of a poorly water soluble HIV-1 protease inhibitor incorporated into pH-sensitive particles: effect of the particle size and nutritional state. J Control Release 68(2):291–298CrossRefGoogle Scholar
  43. 43.
    Vinogradov S, Batrakova E, Kabanov A (1999) Poly (ethylene glycol)–polyethyleneimine NanoGel™ particles: novel drug delivery systems for antisense oligonucleotides. Colloids Surf B 16(1):291–304CrossRefGoogle Scholar
  44. 44.
    Sutton D, Durand R, Shuai X, Gao J (2006) Poly (D, L‐lactide‐co‐glycolide)/poly (ethylenimine) blend matrix system for pH sensitive drug delivery. J Appl Polym Sci 100(1):89–96CrossRefGoogle Scholar
  45. 45.
    Shi S, Shi K, Tan L, Qu Y, Shen G, Chu B, Zhang S, Su X, Li X, Wei Y (2014) The use of cationic MPEG-PCL-g-PEI micelles for co-delivery of Msurvivin T34A gene and doxorubicin. Biomaterials 35(15):4536–4547CrossRefGoogle Scholar
  46. 46.
    Sonaje K, Lin Y-H, Juang J-H, Wey S-P, Chen C-T, Sung H-W (2009) In vivo evaluation of safety and efficacy of self-assembled nanoparticles for oral insulin delivery. Biomaterials 30(12):2329–2339CrossRefGoogle Scholar
  47. 47.
    Boyer C, Bulmus V, Davis TP, Ladmiral V, Liu J, Perrier SB (2009) Bioapplications of RAFT polymerization. Chem Rev 109(11):5402–5436CrossRefGoogle Scholar
  48. 48.
    Zhang S, Zou J, Zhang F, Elsabahy M, Felder SE, Zhu J, Pochan DJ, Wooley KL (2012) Rapid and versatile construction of diverse and functional nanostructures derived from a polyphosphoester-based biomimetic block copolymer system. J Am Chem Soc 134(44):18467–18474CrossRefGoogle Scholar
  49. 49.
    Cheng R, Meng F, Deng C, Klok H-A, Zhong Z (2013) Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials 34(14):3647–3657CrossRefGoogle Scholar
  50. 50.
    Schilli CM, Zhang M, Rizzardo E, Thang SH, Chong Y, Edwards K, Karlsson G, Müller AH (2004) A new double-responsive block copolymer synthesized via RAFT polymerization: poly (N-isopropylacrylamide)-block-poly (acrylic acid). Macromolecules 37(21):7861–7866CrossRefGoogle Scholar
  51. 51.
    Wei H, Zhang X-Z, Cheng H, Chen W-Q, Cheng S-X, Zhuo R-X (2006) Self-assembled thermo-and pH responsive micelles of poly (10-undecenoic acid-b-N-isopropylacrylamide) for drug delivery. J Control Release 116(3):266–274CrossRefGoogle Scholar
  52. 52.
    Soppimath KS, Liu LH, Seow WY, Liu SQ, Powell R, Chan P, Yang YY (2007) Multifunctional core/shell nanoparticles self-assembled from pH-induced thermosensitive polymers for targeted intracellular anticancer drug delivery. Adv Funct Mater 17(3):355–362CrossRefGoogle Scholar
  53. 53.
    Zhang L, Guo R, Yang M, Jiang X, Liu B (2007) Thermo and pH dual‐responsive nanoparticles for anti‐cancer drug delivery. Adv Mater 19(19):2988–2992CrossRefGoogle Scholar
  54. 54.
    Lo C-L, Lin K-M, Hsiue G-H (2005) Preparation and characterization of intelligent core-shell nanoparticles based on poly (D, L-lactide)-g-poly (N-isopropyl acrylamide-co-methacrylic acid). J Control Release 104(3):477–488CrossRefGoogle Scholar
  55. 55.
    Chen Y-C, Liao L-C, Lu P-L, Lo C-L, Tsai H-C, Huang C-Y, Wei K-C, Yen T-C, Hsiue G-H (2012) The accumulation of dual pH and temperature responsive micelles in tumors. Biomaterials 33(18):4576–4588CrossRefGoogle Scholar
  56. 56.
    Johnson RP, Jeong YI, John JV, Chung C-W, Kang DH, Selvaraj M, Suh H, Kim I (2013) Dual stimuli-responsive poly (N-isopropylacrylamide)-b-poly (L-histidine) chimeric materials for the controlled delivery of doxorubicin into liver carcinoma. Biomacromolecules 14(5):1434–1443CrossRefGoogle Scholar
  57. 57.
    Zhang X, Monge S, In M, Giani O, Robin J-J (2013) Thermo-and pH-sensitive aggregation behavior of PDEAm-b-P (l-lysine) double hydrophilic block copolymers in aqueous solution. Soft Matter 9(4):1301–1309CrossRefGoogle Scholar
  58. 58.
    Ahmed EM (2015) Hydrogel: preparation, characterization, and applications. A review. J Adv Res 6(2):105–121CrossRefGoogle Scholar
  59. 59.
    Lim HL, Hwang Y, Kar M, Varghese S (2014) Smart hydrogels as functional biomimetic systems. Biomater Sci 2(5):603–618CrossRefGoogle Scholar
  60. 60.
    Hamidi M, Azadi A, Rafiei P (2008) Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 60(15):1638–1649CrossRefGoogle Scholar
  61. 61.
    de las Heras Alarcón C, Pennadam S, Alexander C (2005) Stimuli responsive polymers for biomedical applications. Chem Soc Rev 34(3):276–285CrossRefGoogle Scholar
  62. 62.
    Qiu Y, Park K (2012) Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev 64:49–60CrossRefGoogle Scholar
  63. 63.
    Zha L, Banik B, Alexis F (2011) Stimulus responsive nanogels for drug delivery. Soft Matter 7(13):5908–5916CrossRefGoogle Scholar
  64. 64.
    Eckmann D, Composto R, Tsourkas A, Muzykantov V (2014) Nanogel carrier design for targeted drug delivery. J Mater Chem B 2(46):8085–8097CrossRefGoogle Scholar
  65. 65.
    An Z, Qiu Q, Liu G (2011) Synthesis of architecturally well-defined nanogels via RAFT polymerization for potential bioapplications. Chem Commun 47(46):12424–12440CrossRefGoogle Scholar
  66. 66.
    Oh JK, Drumright R, Siegwart DJ, Matyjaszewski K (2008) The development of microgels/nanogels for drug delivery applications. Prog Polym Sci 33(4):448–477CrossRefGoogle Scholar
  67. 67.
    Keerl M, Smirnovas V, Winter R, Richtering W (2008) Interplay between hydrogen bonding and macromolecular architecture leading to unusual phase behavior in thermosensitive microgels. Angew Chem 120(2):344–347CrossRefGoogle Scholar
  68. 68.
    Pelton R (2000) Temperature-sensitive aqueous microgels. Adv Colloid Interface Sci 85(1):1–33CrossRefGoogle Scholar
  69. 69.
    Katono H, Maruyama A, Sanui K, Ogata N, Okano T, Sakurai Y (1991) Thermo-responsive swelling and drug release switching of interpenetrating polymer networks composed of poly (acrylamide-co-butyl methacrylate) and poly (acrylic acid). J Control Release 16(1):215–227CrossRefGoogle Scholar
  70. 70.
    Zha L, Hu J, Wang C, Fu S, Elaissari A, Zhang Y (2002) Preparation and characterization of poly (N-isopropylacrylamide-co-dimethylaminoethyl methacrylate) microgel latexes. Colloid Polym Sci 280(1):1–6CrossRefGoogle Scholar
  71. 71.
    Bae YH, Okano T, Hsu R, Kim SW (1987) Thermo‐sensitive polymers as on‐off switches for drug release. Makromol Chem Rapid Commun 8(10):481–485CrossRefGoogle Scholar
  72. 72.
    Bromberg LE, Ron ES (1998) Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. Adv Drug Deliv Rev 31(3):197–221CrossRefGoogle Scholar
  73. 73.
    Jeong B, Bae YH, Lee DS, Kim SW (1997) Biodegradable block copolymers as injectable drug-delivery systems. Nature 388(6645):860–862CrossRefGoogle Scholar
  74. 74.
    Chang C, Wang Z-C, Quan C-Y, Cheng H, Cheng S-X, Zhang X-Z, Zhuo R-X (2007) Fabrication of a novel pH-sensitive glutaraldehyde cross-linked pectin nanogel for drug delivery. J Biomater Sci Polym Ed 18(12):1591–1599Google Scholar
  75. 75.
    Sethuraman VA, Na K, Bae YH (2006) pH-responsive sulfonamide/PEI system for tumor specific gene delivery: an in vitro study. Biomacromolecules 7(1):64–70CrossRefGoogle Scholar
  76. 76.
    Chen Y, Chen Y, Nan J, Wang C, Chu F (2012) Hollow poly (N‐isopropylacrylamide)‐co‐poly (acrylic acid) microgels with high loading capacity for drugs. J Appl Polym Sci 124(6):4678–4685Google Scholar
  77. 77.
    Dai H, Chen Q, Qin H, Guan Y, Shen D, Hua Y, Tang Y, Xu J (2006) A temperature-responsive copolymer hydrogel in controlled drug delivery. Macromolecules 39(19):6584–6589CrossRefGoogle Scholar
  78. 78.
    Yin X, Hoffman AS, Stayton PS (2006) Poly (N-isopropylacrylamide-co-propylacrylic acid) copolymers that respond sharply to temperature and pH. Biomacromolecules 7(5):1381–1385CrossRefGoogle Scholar
  79. 79.
    Bao H, Li L, Gan LH, Ping Y, Li J, Ravi P (2010) Thermo-and pH-responsive association behavior of dual hydrophilic graft chitosan terpolymer synthesized via ATRP and click chemistry. Macromolecules 43(13):5679–5687CrossRefGoogle Scholar
  80. 80.
    Thévenot J, Oliveira H, Sandre O, Lecommandoux S (2013) Magnetic responsive polymer composite materials. Chem Soc Rev 42(17):7099–7116CrossRefGoogle Scholar
  81. 81.
    Kumar CS, Mohammad F (2011) Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. Adv Drug Deliv Rev 63(9):789–808CrossRefGoogle Scholar
  82. 82.
    Xie J, Liu G, Eden HS, Ai H, Chen X (2011) Surface-engineered magnetic nanoparticle platforms for cancer imaging and therapy. Acc Chem Res 44(10):883–892CrossRefGoogle Scholar
  83. 83.
    Liu T-Y, Hu S-H, Liu D-M, Chen S-Y, Chen I-W (2009) Biomedical nanoparticle carriers with combined thermal and magnetic responses. Nano Today 4(1):52–65CrossRefGoogle Scholar
  84. 84.
    Medeiros S, Santos A, Fessi H, Elaissari A (2011) Stimuli-responsive magnetic particles for biomedical applications. Int J Pharm 403(1):139–161CrossRefGoogle Scholar
  85. 85.
    Chen J-P, Su D-R (2001) Latex particles with thermo‐flocculation and magnetic properties for immobilization of α‐chymotrypsin. Biotechnol Prog 17(2):369–375CrossRefGoogle Scholar
  86. 86.
    Satarkar NS, Hilt JZ (2008) Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release. J Control Release 130(3):246–251CrossRefGoogle Scholar
  87. 87.
    Yuan Q, Venkatasubramanian R, Hein S, Misra R (2008) A stimulus-responsive magnetic nanoparticle drug carrier: magnetite encapsulated by chitosan-grafted-copolymer. Acta Biomater 4(4):1024–1037CrossRefGoogle Scholar
  88. 88.
    Jordan A, Wust P, Fähling H, John W, Hinz A, Felix R (2009) Inductive heating of ferrimagnetic particles and magnetic fluids: physical evaluation of their potential for hyperthermia. Int J Hyperthermia 25(7):499–511CrossRefGoogle Scholar
  89. 89.
    Louguet S, Rousseau B, Epherre R, Guidolin N, Goglio G, Mornet S, Duguet E, Lecommandoux S, Schatz C (2012) Thermoresponsive polymer brush-functionalized magnetic manganite nanoparticles for remotely triggered drug release. Polym Chem 3(6):1408–1417CrossRefGoogle Scholar
  90. 90.
    Guo M, Yan Y, Zhang H, Yan H, Cao Y, Liu K, Wan S, Huang J, Yue W (2008) Magnetic and pH-responsive nanocarriers with multilayer core–shell architecture for anticancer drug delivery. J Mater Chem 18(42):5104–5112CrossRefGoogle Scholar
  91. 91.
    Kohler N, Sun C, Wang J, Zhang M (2005) Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells. Langmuir 21(19):8858–8864CrossRefGoogle Scholar
  92. 92.
    Pourjavadi A, Hosseini SH, Alizadeh M, Bennett C (2014) Magnetic pH-responsive nanocarrier with long spacer length and high colloidal stability for controlled delivery of doxorubicin. Colloids Surf B 116:49–54CrossRefGoogle Scholar
  93. 93.
    Fan T, Li M, Wu X, Li M, Wu Y (2011) Preparation of thermoresponsive and pH-sensitivity polymer magnetic hydrogel nanospheres as anticancer drug carriers. Colloids Surf B 88(2):593–600CrossRefGoogle Scholar
  94. 94.
    Tziveleka LA, Bilalis P, Chatzipavlidis A, Boukos N, Kordas G (2014) Development of multiple stimuli responsive magnetic polymer nanocontainers as efficient drug delivery systems. Macromol Biosci 14(1):131–141CrossRefGoogle Scholar
  95. 95.
    Hoffmann F, Cornelius M, Morell J, Fröba M (2006) Silica‐based mesoporous organic–inorganic hybrid materials. Angew Chem Int Ed 45(20):3216–3251CrossRefGoogle Scholar
  96. 96.
    Unger K, Kumar D, Grün M, Büchel G, Lüdtke S, Adam T, Schumacher K, Renker S (2000) Synthesis of spherical porous silicas in the micron and submicron size range: challenges and opportunities for miniaturized high-resolution chromatographic and electrokinetic separations. J Chromatogr A 892(1):47–55CrossRefGoogle Scholar
  97. 97.
    Grün M, Lauer I, Unger KK (1997) The synthesis of micrometer‐and submicrometer‐size spheres of ordered mesoporous oxide MCM‐41. Adv Mater 9(3):254–257CrossRefGoogle Scholar
  98. 98.
    Alothman ZA (2012) A review: fundamental aspects of silicate mesoporous materials. Materials 5(12):2874–2902CrossRefGoogle Scholar
  99. 99.
    Sierra I, Pérez-Quintanilla D (2013) Heavy metal complexation on hybrid mesoporous silicas: an approach to analytical applications. Chem Soc Rev 42(9):3792–3807CrossRefGoogle Scholar
  100. 100.
    Knezevic N, Durand J-O (2014) Large pore mesoporous silica nanomaterials for application in delivery of biomolecules. Nanoscale 7(6):2199–2209CrossRefGoogle Scholar
  101. 101.
    Farjadian F, Ahmadpour P, Samani SM, Hosseini M (2015) Controlled size synthesis and application of nanosphere MCM-41 as potent adsorber of drugs: a novel approach to new antidote agent for intoxication. Microporous Mesoporous Mater 213:30–39CrossRefGoogle Scholar
  102. 102.
    Popat A, Hartono SB, Stahr F, Liu J, Qiao SZ, Lu GQM (2011) Mesoporous silica nanoparticles for bioadsorption, enzyme immobilisation, and delivery carriers. Nanoscale 3(7):2801–2818CrossRefGoogle Scholar
  103. 103.
    Wang L, Zhao W, Tan W (2008) Bioconjugated silica nanoparticles: development and applications. Nano Res 1(2):99–115CrossRefGoogle Scholar
  104. 104.
    Knežević NŽ, Ruiz-Hernández E, Hennink WE, Vallet-Regí M (2013) Magnetic mesoporous silica-based core/shell nanoparticles for biomedical applications. RSC Adv 3(25):9584–9593CrossRefGoogle Scholar
  105. 105.
    Park C, Oh K, Lee SC, Kim C (2007) Controlled release of guest molecules from mesoporous silica particles based on a pH‐responsive polypseudorotaxane motif. Angew Chem Int Ed 46(9):1455–1457CrossRefGoogle Scholar
  106. 106.
    Colilla M, González B, Vallet-Regí M (2013) Mesoporous silica nanoparticles for the design of smart delivery nanodevices. Biomater Sci 1(2):114–134CrossRefGoogle Scholar
  107. 107.
    Owens DE, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307(1):93–102CrossRefGoogle Scholar
  108. 108.
    Lin Y-S, Hung Y, Su J-K, Lee R, Chang C, Lin M-L, Mou C-Y (2004) Gadolinium (III)-incorporated nanosized mesoporous silica as potential magnetic resonance imaging contrast agents. J Phys Chem B 108(40):15608–15611CrossRefGoogle Scholar
  109. 109.
    Hsiao JK, Tsai CP, Chung TH, Hung Y, Yao M, Liu HM, Mou CY, Yang CS, Chen YC, Huang DM (2008) Mesoporous silica nanoparticles as a delivery system of gadolinium for effective human stem cell tracking. Small 4(9):1445–1452CrossRefGoogle Scholar
  110. 110.
    Zhou Z, Zhu S, Zhang D (2007) Grafting of thermo-responsive polymer inside mesoporous silica with large pore size using ATRP and investigation of its use in drug release. J Mater Chem 17(23):2428–2433CrossRefGoogle Scholar
  111. 111.
    Aznar E, Mondragón L, Ros‐Lis JV, Sancenón F, Marcos MD, Martínez-Máñez R, Soto J, Pérez-Payá E, Amorós P (2011) Finely tuned temperature‐controlled cargo release using paraffin‐capped mesoporous silica nanoparticles. Angew Chem 123(47):11368–11371CrossRefGoogle Scholar
  112. 112.
    Popat A, Liu J, Lu GQM, Qiao SZ (2012) A pH-responsive drug delivery system based on chitosan coated mesoporous silica nanoparticles. J Mater Chem 22(22):11173–11178CrossRefGoogle Scholar
  113. 113.
    You Y-Z, Kalebaila KK, Brock SL (2008) Temperature-controlled uptake and release in PNIPAM-modified porous silica nanoparticles. Chem Mater 20(10):3354–3359CrossRefGoogle Scholar
  114. 114.
    Wu X, Wang Z, Zhu D, Zong S, Yang L, Zhong Y, Cui Y (2013) pH and thermo dual-stimuli-responsive drug carrier based on mesoporous silica nanoparticles encapsulated in a copolymer–lipid bilayer. ACS Appl Mater Interfaces 5(21):10895–10903CrossRefGoogle Scholar
  115. 115.
    Casasús R, Climent E, Marcos MD, Martínez-Máñez R, Sancenón F, Soto J, Amorós P, Cano J, Ruiz E (2008) Dual aperture control on pH-and anion-driven supramolecular nanoscopic hybrid gate-like ensembles. J Am Chem Soc 130(6):1903–1917CrossRefGoogle Scholar
  116. 116.
    Chang B, Sha X, Guo J, Jiao Y, Wang C, Yang W (2011) Thermo and pH dual responsive, polymer shell coated, magnetic mesoporous silica nanoparticles for controlled drug release. J Mater Chem 21(25):9239–9247CrossRefGoogle Scholar
  117. 117.
    Dykman L, Khlebtsov N (2012) Gold nanoparticles in biomedical applications: recent advances and perspectives. Chem Soc Rev 41(6):2256–2282CrossRefGoogle Scholar
  118. 118.
    Zhang L, Li Y, Jimmy CY (2014) Chemical modification of inorganic nanostructures for targeted and controlled drug delivery in cancer treatment. J Mater Chem B 2(5):452–470CrossRefGoogle Scholar
  119. 119.
    Zeng S, Yong K-T, Roy I, Dinh X-Q, Yu X, Luan F (2011) A review on functionalized gold nanoparticles for biosensing applications. Plasmonics 6(3):491–506CrossRefGoogle Scholar
  120. 120.
    Beija M, Marty J-D, Destarac M (2011) Thermoresponsive poly (N-vinyl caprolactam)-coated gold nanoparticles: sharp reversible response and easy tunability. Chem Commun 47(10):2826–2828CrossRefGoogle Scholar
  121. 121.
    Contreras-Cáceres R, Sánchez-Iglesias A, Karg M, Pastoriza-Santos I, Pérez-Juste J, Pacifico J, Hellweg T, Fernández-Barbero A, Liz-Marzán LM (2008) Encapsulation and growth of gold nanoparticles in thermoresponsive microgels. Adv Mater 20(9):1666–1670CrossRefGoogle Scholar
  122. 122.
    Liu J, Detrembleur C, Hurtgen M, Debuigne A, De Pauw-Gillet M-C, Mornet S, Duguet E, Jérôme C (2014) Thermo-responsive gold/poly (vinyl alcohol)-b-poly (N-vinylcaprolactam) core–corona nanoparticles as a drug delivery system. Polym Chem 5(18):5289–5299CrossRefGoogle Scholar
  123. 123.
    Li D, Cui Y, Wang K, He Q, Yan X, Li J (2007) Thermosensitive nanostructures comprising gold nanoparticles grafted with block copolymers. Adv Funct Mater 17(16):3134–3140CrossRefGoogle Scholar
  124. 124.
    Genson KL, Holzmueller J, Jiang C, Xu J, Gibson JD, Zubarev ER, Tsukruk VV (2006) Langmuir-Blodgett monolayers of gold nanoparticles with amphiphilic shells from V-shaped binary polymer arms. Langmuir 22(16):7011–7015CrossRefGoogle Scholar
  125. 125.
    Popescu M-T, Tsitsilianis C (2013) Controlled delivery of functionalized gold nanoparticles by pH-sensitive polymersomes. ACS Macro Lett 2(3):222–225CrossRefGoogle Scholar
  126. 126.
    Yavuz MS, Cheng Y, Chen J, Cobley CM, Zhang Q, Rycenga M, Xie J, Kim C, Song KH, Schwartz AG (2009) Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nat Mater 8(12):935–939CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Manufacturing and Industrial Engineering Department, College of Engineering and Computer ScienceThe University of Texas – Rio Grande ValleyEdinburgUSA
  2. 2.Pharmaceutical Sciences Research Center, School of PharmacyShiraz University of Medical SciencesShirazIran

Personalised recommendations