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Intracellular Delivery II pp 55–91Cite as

Stimuli-Responsive Polymeric Nanocarriers as Promising Drug and Gene Delivery Systems

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Part of the book series: Fundamental Biomedical Technologies ((FBMT,volume 7))

Abstract

Polymeric nanocarriers have emerged as promising drug delivery vehicles owing to their potential to selectively deliver the active agents to the disease sites through various targeting mechanisms, while minimizing the side effects. To realize more enhanced therapeutic effect, it is also highly essential to impart specific release mechanism into the nanocarriers in addition to the targeting capabilities. In this regard, stimuli-sensitive or smart polymeric nanocarriers that are responsive to inherent (e.g. pH, temperature, redox, hypoxia, enzymes, and reactive oxygen species) or external stimuli (e.g. light, ultrasound or magnetic) have received enormous attention because of their ability to control the drug release profile in a desirable fashion at the target site of action. The primary focus of this chapter is to highlight the recent advances of various stimuli-responsive nanocarriers that have been developed for a more efficient drug and gene delivery.

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Abbreviations

AGA:

Acrylglucosamine

APBA:

Acrylamidephenylboronic acid

AspPBA:

Aspartamidophenylboronic acid

ATRP:

Atom transfer radical polymerization

BAC:

N,N-Bis(acryloyl) cystamine

C18:

n-Octadecane amine

CPT:

Camptothecin

DET:

N-(2-Aminoethyl)-2-aminoethyl group

Dex-LA:

Dextran-lipoic acid

DNQ:

2-Diazo-1,2-Napthoquinone

DOX:

Doxorubicin

DTT:

d,l-Dithiothreitol

EPR:

Enhanced permeation and retention

Gal:

Galactose

GI:

Gastrointestinal

GSH:

Glutathione

HA:

Hyaluronic acid

HMAAM:

Hydroxymethylacrylamide

HP:

Hydrotropic polymer

Hyals:

Hyaluronidases

LCST:

Low critical solution temperature

MC:

Merocyanine

MMPs:

Matrix metalloproteinases

MTX:

Methotrexate

NAS:

N-Acryloxysuccinimide

NBC-NCA:

S-(O-Nitrobenzyl)-l-cysteine) N-carboxyanhydride

ND:

Polyester nanodendron

NIPAM:

N-Isopropylacrylamide

NMP:

Nitric oxide mediated radical polymerization

OG:

Oregon green 488

P(Asp):

Poly(aspartamide)

P(HPMA-Lacn):

Poly(2-hydroxypropyl methacrylate lactate)

P4VP:

Poly(4-vinylpyridine)

PAA:

Poly(acrylic acid)

PAMAM:

Poly(amido amine)

PAzoMA:

Polymethacrylate bearing azobenzene side groups

PBA:

Phenylboronic acid

PBLG:

Poly(γ-benzyl l-glutamate)

PBMA:

Poly(butylmethacrylate)

PCL:

Poly(caprolactone)

PDEA:

Poly(diethylamino)ethyl methacrylate

PDLLA:

Poly(d,l-lactide)

PDMAEMA:

Poly(dimethylaminoethyl methacrylate)

PEEP:

Poly(ethyl ethylene phosphate)

PEG:

Poly(ethylene glycol)

PEI:

Poly(ethylene imine)

PEO:

Poly(ethylene oxide)

P-HA-NPs:

PEGylated HA nanoparticles

PHB:

Poly[(R)-3-hydroxybutyrate]

PHis:

Poly(l-histidine)

PLGA:

Poly(lactic-co-glycolic) acid

PLL:

Poly(l-lysine)

PLLA:

Poly(l-lactic acid)

PMAA:

Poly(methacrylic acid)

PNIPAM:

Poly(N-isopropylacrylamide)

PPS:

Poly(propylene sulfide)

PS:

Polystyrene

PTX:

Paclitaxel

RAFT:

Reversible addition-fragmentation chain transfer

ROMP:

Ring opening metathesis polymerization

SP:

Spiropyran

UCNPs:

Upconverting nanoparticles

UCST:

Upper critical solution temperature

References

  • Agarwal S, Zhang Y, Maji S, Greiner A (2012) PDMAEMA based gene delivery materials. Mater Today 15(9):388–393

    CAS  Google Scholar 

  • Akimoto J, Nakayama M, Sakai K, Okano T (2009) Temperature-induced intracellular uptake of thermoresponsive polymeric micelles. Biomacromolecules 10(6):1331–1336

    CAS  PubMed  Google Scholar 

  • 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):926–935

    CAS  PubMed  Google Scholar 

  • Allen TM (2002) Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2(10):750–763

    CAS  PubMed  Google Scholar 

  • Asokan A, Cho MJ (2002) Exploitation of intracellular pH gradients in the cellular delivery of macromolecules. J Pharm Sci 91(4):903–913

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  • Blasco E, Serrano JL, Piñol M, Oriol L (2013) Light responsive vesicles based on linear-dendritic block copolymers using azobenzene-aliphatic codendrons. Macromolecules 46(15):5951–5960

    CAS  Google Scholar 

  • Bratlie KM, York RL, Invernale MA, Langer R, Anderson DG (2012) Materials for diabetes therapeutics. Adv Healthc Mater 1(3):267–284

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Cai X-J, Dong H-Q, Xia W-J, Wen H-Y, Li X-Q, Yu J-H, Li Y-Y, Shi D-L (2011) Glutathione-mediated shedding of PEG layers based on disulfide-linked catiomers for DNA delivery. J Mater Chem 21(38):14639–14645

    CAS  Google Scholar 

  • 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(2–3):157–164

    CAS  Google Scholar 

  • Cerritelli S, Velluto D, Hubbell JA (2007) PEG-SS-PPS: reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery. Biomacromolecules 8(6):1966–1972

    CAS  PubMed  Google Scholar 

  • Chau Y, Tan FE, Langer R (2004) Synthesis and characterization of dextran-peptide-methotrexate conjugates for tumor targeting via mediation by matrix metalloproteinase II and matrix metalloproteinase IX. Bioconjug Chem 15(4):931–941

    CAS  PubMed  Google Scholar 

  • Chen C-J, Liu G-Y, Shi Y-T, Zhu C-S, Pang S-P, Liu X-S, Ji J (2011) Biocompatible micelles based on comb-like PEG derivates: formation, characterization, and photo-responsiveness. Macromol Rapid Commun 32(14):1077–1081

    CAS  PubMed  Google Scholar 

  • Cheng C, Wei H, Shi B-X, Cheng H, Li C, Gu Z-W, Cheng S-X, Zhang X-Z, Zhuo R-X (2008) Biotinylated thermoresponsive micelle self-assembled from double-hydrophilic block copolymer for drug delivery and tumor target. Biomaterials 29(4):497–505

    CAS  PubMed  Google Scholar 

  • Cheng C, Zhang X, Wang Y, Sun L, Li C (2012) Phenylboronic acid-containing block copolymers: synthesis, self-assembly, and application for intracellular delivery of proteins. New J Chem 36(6):1413–1421

    CAS  Google Scholar 

  • Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z (2011) Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery. J Control Release 152(1):2–12

    CAS  PubMed  Google Scholar 

  • Chilkoti A, Dreher MR, Meyer DE, Raucher D (2002) Targeted drug delivery by thermally responsive polymers. Adv Drug Deliv Rev 54(5):613–630

    CAS  PubMed  Google Scholar 

  • Choi KY, Chung H, Min KH, Yoon HY, Kim K, Park JH, Kwon IC, Jeong SY (2010) Self-assembled hyaluronic acid nanoparticles for active tumor targeting. Biomaterials 31(1):106–114

    CAS  PubMed  Google Scholar 

  • Choi KY, Saravanakumar G, Park JH, Park K (2012) Hyaluronic acid-based nanocarriers for intracellular targeting: interfacial interactions with proteins in cancer. Colloids Surf B Biointerfaces 99:82–94

    CAS  PubMed Central  PubMed  Google Scholar 

  • Choi KY, Yoon HY, Kim J-H, Bae SM, Park R-W, Kang YM, Kim I-S, Kwon IC, Choi K, Jeong SY, Kim K, Park JH (2011) Smart nanocarrier based on PEGylated hyaluronic acid for cancer therapy. ACS Nano 5(11):8591–8599

    CAS  PubMed  Google Scholar 

  • Christensen LV, Chang C-W, Kim WJ, Kim SW, Zhong Z, Lin C, Engbersen JFJ, Feijen J (2006) Reducible poly(amido ethylenimine)s designed for triggered intracellular gene delivery. Bioconjug Chem 17(5):1233–1240

    CAS  PubMed  Google Scholar 

  • Chung JE, 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(1–3):119–130

    CAS  PubMed  Google Scholar 

  • Chung JE, Yokoyama M, Okano T (2000) Inner core segment design for drug delivery control of thermo-responsive polymeric micelles. J Control Release 65(1–2):93–103

    CAS  PubMed  Google Scholar 

  • Dan K, Ghosh S (2013) One-pot synthesis of an acid-labile amphiphilic triblock copolymer and its pH-responsive vesicular assembly. Angew Chem Int Ed 52(28):7300–7305

    CAS  Google Scholar 

  • Dan K, Pan R, Ghosh S (2010) Aggregation and pH responsive disassembly of a new acid-labile surfactant synthesized by thiol-acrylate Michael addition reaction. Langmuir 27(2):612–617

    PubMed  Google Scholar 

  • de la Rica R, Aili D, Stevens MM (2012) Enzyme-responsive nanoparticles for drug release and diagnostics. Adv Drug Deliv Rev 64(11):967–978

    PubMed  Google Scholar 

  • De Smedt S, Demeester J, Hennink W (2000) Cationic polymer based gene delivery systems. Pharm Res 17(2):113–126

    PubMed  Google Scholar 

  • Deng L, Wang G, Ren J, Zhang B, Yan J, Li W, Khashab NM (2012) Enzymatically triggered multifunctional delivery system based on hyaluronic acid micelles. RSC Adv 2(33):12909–12914

    CAS  Google Scholar 

  • Ding C, Gu J, Qu X, Yang Z (2009) Preparation of multifunctional drug carrier for tumor-specific uptake and enhanced intracellular delivery through the conjugation of weak acid labile linker. Bioconjug Chem 20(6):1163–1170

    CAS  PubMed  Google Scholar 

  • Duncan R (2003) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2(5):347–360

    CAS  PubMed  Google Scholar 

  • Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161–174

    CAS  PubMed  Google Scholar 

  • Fomina N, Sankaranarayanan J, Almutairi A (2012) Photochemical mechanisms of light-triggered release from nanocarriers. Adv Drug Deliv Rev 64(11):1005–1020

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gao W, Chan JM, Farokhzad OC (2010) pH-responsive nanoparticles for drug delivery. Mol Pharm 7(6):1913–1920

    CAS  PubMed Central  PubMed  Google Scholar 

  • Green JJ, Langer R, Anderson DG (2008) A combinatorial polymer library approach yields insight into nonviral gene delivery. Acc Chem Res 41(6):749–759

    CAS  PubMed Central  PubMed  Google Scholar 

  • Haag R, Kratz F (2006) Polymer therapeutics: concepts and applications. Angew Chem Int Ed 45(8):1198–1215

    CAS  Google Scholar 

  • He E, Yue CY, Tam KC (2010) Binding and release studies of a cationic drug from a star-shaped four-arm poly(ethylene oxide)-b-poly(methacrylic acid). J Pharm Sci 99(2):782–793

    CAS  PubMed  Google Scholar 

  • Hong C-Y, You Y-Z, Pan C-Y (2004) Synthesis and characterization of well-defined diblock and triblock copolymers of poly(N-isopropylacrylamide) and poly(ethylene oxide). J Polym Sci, Part A: Polym Chem 42(19):4873–4881

    CAS  Google Scholar 

  • Howard KA (2009) Delivery of RNA interference therapeutics using polycation-based nanoparticles. Adv Drug Deliv Rev 61(9):710–720

    CAS  PubMed  Google Scholar 

  • Itaka K, Yamauchi K, Harada A, Nakamura K, Kawaguchi H, Kataoka K (2003) Polyion complex micelles from plasmid DNA and poly(ethylene glycol)–poly(l-lysine) block copolymer as serum-tolerable polyplex system: physicochemical properties of micelles relevant to gene transfection efficiency. Biomaterials 24(24):4495–4506

    CAS  PubMed  Google Scholar 

  • Jia L, Li Z, Zhang D, Zhang Q, Shen J, Guo H, Tian X, Liu G, Zheng D, Qi L (2013) Redox-responsive catiomer based on PEG-ss-chitosan oligosaccharide-ss-polyethylenimine copolymer for effective gene delivery. Polym Chem 4(1):156–165

    CAS  Google Scholar 

  • Jiang J, Tong X, Morris D, Zhao Y (2006) Toward photocontrolled release using light-dissociable block copolymer micelles. Macromolecules 39(13):4633–4640

    CAS  Google Scholar 

  • Jiang J, Tong X, Zhao Y (2005) A new design for light-breakable polymer micelles. J Am Chem Soc 127(23):8290–8291

    CAS  PubMed  Google Scholar 

  • Jin X, Zhang X, Wu Z, Teng D, Zhang X, Wang Y, Wang Z, Li C (2009) Amphiphilic random glycopolymer based on phenylboronic acid: synthesis, characterization, and potential as glucose-sensitive matrix. Biomacromolecules 10(6):1337–1345

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Kamaly N, Xiao Z, Valencia PM, Radovic-Moreno AF, Farokhzad OC (2012) Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev 41(7):2971–3010

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kataoka K, Miyazaki H, Bunya M, Okano T, Sakurai Y (1998) Totally synthetic polymer gels responding to external glucose concentration: their preparation and application to on–off regulation of insulin release. J Am Chem Soc 120(48):12694–12695

    CAS  Google Scholar 

  • Kim H, Kang YJ, Kang S, Kim KT (2012) Monosaccharide-responsive release of insulin from polymersomes of polyboroxole block copolymers at neutral pH. J Am Chem Soc 134(9):4030–4033

    CAS  PubMed  Google Scholar 

  • Kim S, Kim JY, Huh KM, Acharya G, Park K (2008) Hydrotropic polymer micelles containing acrylic acid moieties for oral delivery of paclitaxel. J Control Release 132(3):222–229

    CAS  PubMed Central  PubMed  Google Scholar 

  • Knorr V, Allmendinger L, Walker GF, Paintner FF, Wagner E (2007) An acetal-based PEGylation reagent for pH-sensitive shielding of DNA polyplexes. Bioconjug Chem 18(4):1218–1225

    CAS  PubMed  Google Scholar 

  • Koo H, Huh MS, Sun I-C, Yuk SH, Choi K, Kim K, Kwon IC (2011) In vivo targeted delivery of nanoparticles for theranosis. Acc Chem Res 44(10):1018–1028

    CAS  PubMed  Google Scholar 

  • Kotharangannagari VK, Sánchez-Ferrer A, Ruokolainen J, Mezzenga R (2011) Photoresponsive reversible aggregation and dissolution of rod–coil polypeptide diblock copolymers. Macromolecules 44(12):4569–4573

    CAS  Google Scholar 

  • Kuppusamy P, Li H, Ilangovan G, Cardounel AJ, Zweier JL, Yamada K, Krishna MC, Mitchell JB (2002) Noninvasive imaging of tumor redox status and its modification by tissue glutathione levels. Cancer Res 62(1):307–312

    CAS  PubMed  Google Scholar 

  • Lee ES, Gao Z, Kim D, Park K, Kwon IC, Bae YH (2008) Super pH-sensitive multifunctional polymeric micelle for tumor pH(e) specific TAT exposure and multidrug resistance. J Control Release 129(3):228–236

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee ES, Na K, Bae YH (2005) Super pH-sensitive multifunctional polymeric micelle. Nano Lett 5(2):325–329

    CAS  PubMed  Google Scholar 

  • Lee GY, Park K, Kim SY, Byun Y (2007) MMPs-specific PEGylated peptide–DOX conjugate micelles that can contain free doxorubicin. Eur J Pharm Biopharm 67(3):646–654

    CAS  PubMed  Google Scholar 

  • Lee JS, Groothuis T, Cusan C, Mink D, Feijen J (2011) Lysosomally cleavable peptide-containing polymersomes modified with anti-EGFR antibody for systemic cancer chemotherapy. Biomaterials 32(34):9144–9153

    CAS  PubMed  Google Scholar 

  • Lee S-Y, Huh MS, Lee S, Lee SJ, Chung H, Park JH, Oh Y-K, Choi K, Kim K, Kwon IC (2010) Stability and cellular uptake of polymerized siRNA (poly-siRNA)/polyethylenimine (PEI) complexes for efficient gene silencing. J Control Release 141(3):339–346

    CAS  PubMed  Google Scholar 

  • Li G, Shi L, Ma R, An Y, Huang N (2006a) Formation of complex micelles with double-responsive channels from self-assembly of two diblock copolymers. Angew Chem Int Ed 45(30):4959–4962

    CAS  Google Scholar 

  • Li H, Yu SS, Miteva M, Nelson CE, Werfel T, Giorgio TD, Duvall CL (2013a) Matrix metalloproteinase responsive, proximity-activated polymeric nanoparticles for siRNA delivery. Adv Funct Mater 23(24):3040–3052

    CAS  Google Scholar 

  • Li J, Ge Z, Liu S (2013b) PEG-sheddable polyplex micelles as smart gene carriers based on MMP-cleavable peptide-linked block copolymers. Chem Commun 49(62):6974–6976

    CAS  Google Scholar 

  • Li L-Y, He W-D, Li J, Zhang B-Y, Pan T-T, Sun X-L, Ding Z-L (2010a) Shell-cross-linked micelles from PNIPAM-b-(PLL)2 Y-shaped miktoarm star copolymer as drug carriers. Biomacromolecules 11(7):1882–1890

    CAS  PubMed  Google Scholar 

  • Li S-D, Huang L (2008) Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm 5(4):496–504

    CAS  PubMed  Google Scholar 

  • Li Y-L, Zhu L, Liu Z, Cheng R, Meng F, Cui J-H, Ji S-J, Zhong Z (2009) Reversibly stabilized multifunctional dextran nanoparticles efficiently deliver doxorubicin into the nuclei of cancer cells. Angew Chem Int Ed 48(52):9914–9918

    CAS  Google Scholar 

  • Li Y, Lokitz BS, Armes SP, McCormick CL (2006b) Synthesis of reversible shell cross-linked micelles for controlled release of bioactive agents. Macromolecules 39(8):2726–2728

    CAS  Google Scholar 

  • Li Y, Lokitz BS, McCormick CL (2005) RAFT synthesis of a thermally responsive ABC triblock copolymer incorporating N-acryloxysuccinimide for facile in situ formation of shell cross-linked micelles in aqueous media. Macromolecules 39(1):81–89

    Google Scholar 

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

    CAS  Google Scholar 

  • Lin C, Zhong Z, Lok MC, Jiang X, Hennink WE, Feijen J, Engbersen JFJ (2006) Linear poly(amido amine)s with secondary and tertiary amino groups and variable amounts of disulfide linkages: Synthesis and in vitro gene transfer properties. J Control Release 116(2):130–137

    CAS  PubMed  Google Scholar 

  • Lin S, Du F, Wang Y, Ji S, Liang D, Yu L, Li Z (2007) An acid-labile block copolymer of PDMAEMA and PEG as potential carrier for intelligent gene delivery systems. Biomacromolecules 9(1):109–115

    PubMed  Google Scholar 

  • Liu G, Dong C-M (2012) Photoresponsive poly(S-(o-nitrobenzyl)-l-cysteine)-b-PEO from a l-Cysteine N-Carboxyanhydride monomer: synthesis, self-assembly, and phototriggered drug release. Biomacromolecules 13(5):1573–1583

    CAS  PubMed  Google Scholar 

  • Liu G, Ma R, Ren J, Li Z, Zhang H, Zhang Z, An Y, Shi L (2013) A glucose-responsive complex polymeric micelle enabling repeated on–off release and insulin protection. Soft Matter 9(5):1636–1644

    CAS  Google Scholar 

  • Liu S-Q, Wiradharma N, Gao S-J, Tong YW, Yang Y-Y (2007) Bio-functional micelles self-assembled from a folate-conjugated block copolymer for targeted intracellular delivery of anticancer drugs. Biomaterials 28(7):1423–1433

    CAS  PubMed  Google Scholar 

  • Liu SQ, Tong YW, Yang Y-Y (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

    CAS  PubMed  Google Scholar 

  • Luo S, Xu J, Zhu Z, Wu C, Liu S (2006) Phase transition behavior of unimolecular micelles with thermoresponsive poly(N-isopropylacrylamide) coronas. J Phys Chem B 110(18):9132–9139

    CAS  PubMed  Google Scholar 

  • Ma R, Yang H, Li Z, Liu G, Sun X, Liu X, An Y, Shi L (2012) Phenylboronic acid-based complex micelles with enhanced glucose-responsiveness at physiological pH by complexation with glycopolymer. Biomacromolecules 13(10):3409–3417

    CAS  PubMed  Google Scholar 

  • Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1–2):271–284

    CAS  PubMed  Google Scholar 

  • Matsumoto A, Yoshida R, Kataoka K (2004) Glucose-responsive polymer gel bearing phenylborate derivative as a glucose-sensing moiety operating at the physiological pH. Biomacromolecules 5(3):1038–1045

    CAS  PubMed  Google Scholar 

  • Meng F, Hennink WE, Zhong Z (2009) Reduction-sensitive polymers and bioconjugates for biomedical applications. Biomaterials 30(12):2180–2198

    CAS  PubMed  Google Scholar 

  • Mok H, Lee SH, Park JW, Park TG (2010) Multimeric small interfering ribonucleic acid for highly efficient sequence-specific gene silencing. Nat Mater 9(3):272–278

    CAS  PubMed  Google Scholar 

  • Mok H, Park JW, Park TG (2007) Antisense oligodeoxynucleotide-conjugated hyaluronic acid/protamine nanocomplexes for intracellular gene inhibition. Bioconjug Chem 18(5):1483–1489

    CAS  PubMed  Google Scholar 

  • Nagasaki T, Taniguchi A, Tamagaki S (2003) Photoenhancement of transfection efficiency using novel cationic lipids having a photocleavable spacer. Bioconjug Chem 14(3):513–516

    CAS  PubMed  Google Scholar 

  • Namgung R, Kim WJ (2012) A highly entangled polymeric nanoconstruct assembled by siRNA and its reduction-triggered siRNA release for gene silencing. Small 8(20):3209–3219

    CAS  PubMed  Google Scholar 

  • Oh JK, Siegwart DJ, H-i Lee, Sherwood G, Peteanu L, Hollinger JO, Kataoka K, Matyjaszewski K (2007a) Biodegradable nanogels prepared by atom transfer radical polymerization as potential drug delivery carriers: synthesis, biodegradation, in vitro release, and bioconjugation. J Am Chem Soc 129(18):5939–5945

    CAS  PubMed  Google Scholar 

  • Oh JK, Siegwart DJ, Matyjaszewski K (2007b) Synthesis and biodegradation of nanogels as delivery carriers for carbohydrate drugs. Biomacromolecules 8(11):3326–3331

    CAS  PubMed  Google Scholar 

  • Park JH, Lee S, Kim J-H, Park K, Kim K, Kwon IC (2008) Polymeric nanomedicine for cancer therapy. Prog Polym Sci 33(1):113–137

    Google Scholar 

  • Park JH, Saravanakumar G, Kim K, Kwon IC (2010) Targeted delivery of low molecular drugs using chitosan and its derivatives. Adv Drug Deliv Rev 62(1):28–41

    CAS  PubMed  Google Scholar 

  • Prabaharan M, Grailer JJ, Steeber DA, Gong S (2009) Thermosensitive micelles based on folate-conjugated poly(N-vinylcaprolactam)-block-poly(ethylene glycol) for tumor-targeted drug delivery. Macromol Biosci 9(8):744–753

    CAS  PubMed  Google Scholar 

  • Putnam D, Zelikin AN, Izumrudov VA, Langer R (2003) Polyhistidine–PEG: DNA nanocomposites for gene delivery. Biomaterials 24(24):4425–4433

    CAS  PubMed  Google Scholar 

  • Rao J, Khan A (2013) Enzyme sensitive synthetic polymer micelles based on the azobenzene motif. J Am Chem Soc 135(38):14056–14059

    CAS  PubMed  Google Scholar 

  • Rao NV, Mane S, Kishore A, Das Sarma J, Shunmugam R (2011) Norbornene derived doxorubicin copolymers as drug carriers with pH responsive hydrazone linker. Biomacromolecules 13(1):221–230

    PubMed  Google Scholar 

  • Rezaei SJT, Nabid MR, Niknejad H, Entezami AA (2012) Folate-decorated thermoresponsive micelles based on star-shaped amphiphilic block copolymers for efficient intracellular release of anticancer drugs. Int J Pharm 437(1–2):70–79

    CAS  PubMed  Google Scholar 

  • Rijcken CJ, Snel CJ, Schiffelers RM, van Nostrum CF, Hennink WE (2007a) Hydrolysable core-crosslinked thermosensitive polymeric micelles: synthesis, characterisation and in vivo studies. Biomaterials 28(36):5581–5593

    CAS  PubMed  Google Scholar 

  • Rijcken CJF, Hofman J-W, van Zeeland F, Hennink WE, van Nostrum CF (2007b) Photosensitiser-loaded biodegradable polymeric micelles: preparation, characterisation and in vitro PDT efficacy. J Control Release 124(3):144–153

    CAS  PubMed  Google Scholar 

  • Ryu J-H, Park S, Kim B, Klaikherd A, Russell TP, Thayumanavan S (2009) Highly ordered gold nanotubes using thiols at a cleavable block copolymer interface. J Am Chem Soc 131(29):9870–9871

    CAS  PubMed  Google Scholar 

  • Saeed AO, Magnusson JP, Moradi E, Soliman M, Wang W, Stolnik S, Thurecht KJ, Howdle SM, Alexander C (2011) Modular construction of multifunctional bioresponsive cell-targeted nanoparticles for gene delivery. Bioconjug Chem 22(2):156–168

    CAS  PubMed  Google Scholar 

  • Samuelson LE, Scherer RL, Matrisian LM, McIntyre JO, Bornhop DJ (2013) Synthesis and in vitro efficacy of MMP9-activated nanodendrons. Mol Pharm 10(8):3164–3174

    CAS  PubMed  Google Scholar 

  • Saravanakumar G, Choi KY, Yoon HY, Kim K, Park JH, Kwon IC, Park K (2010) Hydrotropic hyaluronic acid conjugates: synthesis, characterization, and implications as a carrier of paclitaxel. Int J Pharm 394(1–2):154–161

    CAS  PubMed  Google Scholar 

  • Schmaljohann D (2006) Thermo- and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev 58(15):1655–1670

    CAS  PubMed  Google Scholar 

  • Sinha VR, Kumria R (2001) Polysaccharides in colon-specific drug delivery. Int J Pharm 224(1–2):19–38

    CAS  PubMed  Google Scholar 

  • Soga O, van Nostrum CF, Fens M, Rijcken CJF, Schiffelers RM, Storm G, Hennink WE (2005) Thermosensitive and biodegradable polymeric micelles for paclitaxel delivery. J Control Release 103(2):341–353

    CAS  PubMed  Google Scholar 

  • Son S, Namgung R, Kim J, Singha K, Kim WJ (2011) Bioreducible polymers for gene silencing and delivery. Acc Chem Res 45(7):1100–1112

    PubMed  Google Scholar 

  • Son S, Singha K, Kim WJ (2010) Bioreducible BPEI-SS-PEG-cNGR polymer as a tumor targeted nonviral gene carrier. Biomaterials 31(24):6344–6354

    CAS  PubMed  Google Scholar 

  • Son YJ, Jang JS, Cho YW, Chung H, Park RW, Kwon IC, Kim IS, Park JY, Seo SB, Park CR, Jeong SY (2003) Biodistribution and anti-tumor efficacy of doxorubicin loaded glycol-chitosan nanoaggregates by EPR effect. J Control Release 91(1–2):135–145

    CAS  PubMed  Google Scholar 

  • Song N, Liu W, Tu Q, Liu R, Zhang Y, Wang J (2011) Preparation and in vitro properties of redox-responsive polymeric nanoparticles for paclitaxel delivery. Colloids Surf B Biointerfaces 87(2):454–463

    CAS  PubMed  Google Scholar 

  • Sun H, Guo B, Cheng R, Meng F, Liu H, Zhong Z (2009) Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin. Biomaterials 30(31):6358–6366

    CAS  PubMed  Google Scholar 

  • Sun H, Guo B, Li X, Cheng R, Meng F, Liu H, Zhong Z (2010) Shell-sheddable micelles based on dextran-SS-poly(ε-caprolactone) diblock copolymer for efficient intracellular release of doxorubicin. Biomacromolecules 11(4):848–854

    CAS  PubMed  Google Scholar 

  • Sun L, Ma X, Dong C-M, Zhu B, Zhu X (2012) NIR-responsive and lectin-binding doxorubicin-loaded nanomedicine from janus-type dendritic PAMAM amphiphiles. Biomacromolecules 13(11):3581–3591

    CAS  PubMed  Google Scholar 

  • Takae S, Miyata K, Oba M, Ishii T, Nishiyama N, Itaka K, Yamasaki Y, Koyama H, Kataoka K (2008) PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors. J Am Chem Soc 130(18):6001–6009

    CAS  PubMed  Google Scholar 

  • Talelli M, Rijcken CJF, Lammers T, Seevinck PR, Storm G, van Nostrum CF, Hennink WE (2009) Superparamagnetic iron oxide nanoparticles encapsulated in biodegradable thermosensitive polymeric micelles: toward a targeted nanomedicine suitable for image-guided drug delivery. Langmuir 25(4):2060–2067

    CAS  PubMed  Google Scholar 

  • Tang L-Y, Wang Y-C, Li Y, Du J-Z, Wang J (2009) Shell-detachable micelles based on disulfide-linked block copolymer as potential carrier for intracellular drug delivery. Bioconjug Chem 20(6):1095–1099

    CAS  PubMed  Google Scholar 

  • Tang R, Ji W, Panus D, Palumbo RN, Wang C (2011) Block copolymer micelles with acid-labile ortho ester side-chains: synthesis, characterization, and enhanced drug delivery to human glioma cells. J Control Release 151(1):18–27

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thambi T, Yoon HY, Kim K, Kwon IC, Yoo CK, Park JH (2011) Bioreducible block copolymers based on poly(Ethylene Glycol) and poly(γ-Benzyl l-Glutamate) for intracellular delivery of camptothecin. Bioconjug Chem 22(10):1924–1931

    CAS  PubMed  Google Scholar 

  • Tomatsu I, Peng K, Kros A (2011) Photoresponsive hydrogels for biomedical applications. Adv Drug Deliv Rev 63(14–15):1257–1266

    CAS  PubMed  Google Scholar 

  • Tong R, Hemmati HD, Langer R, Kohane DS (2012) Photoswitchable nanoparticles for triggered tissue penetration and drug delivery. J Am Chem Soc 134(21):8848–8855

    CAS  PubMed Central  PubMed  Google Scholar 

  • Walker GF, Fella C, Pelisek J, Fahrmeir J, Boeckle S, Ogris M, Wagner E (2005) Toward synthetic viruses: endosomal pH-triggered deshielding of targeted polyplexes greatly enhances gene transfer in vitro and in vivo. Mol Ther 11(3):418–425

    CAS  PubMed  Google Scholar 

  • Wang G, Tong X, Zhao Y (2004) Preparation of azobenzene-containing amphiphilic diblock copolymers for light-responsive micellar aggregates. Macromolecules 37(24):8911–8917

    CAS  Google Scholar 

  • Wang W, Sun H, Meng F, Ma S, Liu H, Zhong Z (2012) Precise control of intracellular drug release and anti-tumor activity of biodegradable micellar drugs via reduction-sensitive shell-shedding. Soft Matter 8(14):3949–3956

    CAS  Google Scholar 

  • Wang X-Q, Zhang Q (2012) pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs. Eur J Pharm Biopharm 82(2):219–229

    CAS  PubMed  Google Scholar 

  • Wang X, Sun H, Meng F, Cheng R, Deng C, Zhong Z (2013) Galactose-decorated reduction-sensitive degradable chimaeric polymersomes as a multifunctional nanocarrier to efficiently chaperone apoptotic proteins into hepatoma cells. Biomacromolecules 14(8):2873–2882

    CAS  PubMed  Google Scholar 

  • Wang Y-C, Wang F, Sun T-M, 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

    CAS  PubMed  Google Scholar 

  • Wei H, Zhuo R-X, Zhang X-Z (2013) Design and development of polymeric micelles with cleavable links for intracellular drug delivery. Prog Polym Sci 38(3–4):503–535

    CAS  Google Scholar 

  • Wu Q, Wang L, Yu H, Wang J, Chen Z (2011) Organization of glucose-responsive systems and their properties. Chem Rev 111(12):7855–7875

    CAS  PubMed  Google Scholar 

  • Yan B, Boyer J-C, 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

    CAS  PubMed  Google Scholar 

  • Yan J, Ji W, Chen E, Li Z, Liang D (2008) Association and aggregation behavior of poly(ethylene oxide)-b-poly (N-isopropylacrylamide) in aqueous solution. Macromolecules 41(13):4908–4913

    CAS  Google Scholar 

  • Yesilyurt V, Ramireddy R, Thayumanavan S (2011) Photoregulated release of noncovalent guests from dendritic amphiphilic nanocontainers. Angew Chem 123(13):3094–3098

    Google Scholar 

  • You Y-Z, Manickam DS, Zhou Q-H, Oupický D (2007) Reducible poly(2-dimethylaminoethyl methacrylate): synthesis, cytotoxicity, and gene delivery activity. J Control Release 122(3):217–225

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zelzer M, Todd SJ, Hirst AR, McDonald TO, Ulijn RV (2013) Enzyme responsive materials: design strategies and future developments. Biomaterials Science 1(1):11–39

    CAS  Google Scholar 

  • Zeng YI, Pitt WG (2005) Poly(ethylene oxide)-b-poly(N-isopropylacrylamide) nanoparticles with cross-linked cores as drug carriers. J Biomater Sci Polym Ed 16(3):371–380

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang W, Shi L, Wu K, An Y (2005) Thermoresponsive micellization of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) in water. Macromolecules 38(13):5743–5747

    CAS  Google Scholar 

  • Zhao Y (2007) Rational design of light-controllable polymer micelles. Chem Rec 7(5):286–294

    CAS  PubMed  Google Scholar 

  • Zhao Y (2012) Light-responsive block copolymer micelles. Macromolecules 45(9):3647–3657

    CAS  Google Scholar 

  • Zhu C, Zheng M, Meng F, Mickler FM, Ruthardt N, Zhu X, Zhong Z (2012) Reversibly shielded DNA polyplexes based on bioreducible PDMAEMA-SS-PEG-SS-PDMAEMA triblock copolymers mediate markedly enhanced nonviral gene transfection. Biomacromolecules 13(3):769–778

    PubMed  Google Scholar 

  • Zugates GT, Anderson DG, Little SR, Lawhorn IEB, Langer R (2006) Synthesis of poly(β-amino ester)s with thiol-reactive side chains for DNA delivery. J Am Chem Soc 128(39):12726–12734

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Research Center Program of IBS (Institute for Basic Science) in Korea (CA1203-02).

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Authors and Affiliations

  1. Center for Self-Assembly and Complexity, Institute for Basic Science (IBS), and Department of Chemistry Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, South Korea

    Gurusamy Saravanakumar & Won Jong Kim

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  1. Gurusamy Saravanakumar
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  2. Won Jong Kim
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Correspondence to Won Jong Kim .

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Editors and Affiliations

  1. Chemical and Biological Engineering, Vanderbilt University, Nashville, Tennessee, USA

    Aleš Prokop

  2. Chemistry and Materials Engineering, Kansai University, Osaka, Japan

    Yasuhiko Iwasaki

  3. Department of Applied Chemistry, Osaka Prefecture University, Osaka, Japan

    Atsushi Harada

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Saravanakumar, G., Kim, W.J. (2014). Stimuli-Responsive Polymeric Nanocarriers as Promising Drug and Gene Delivery Systems. In: Prokop, A., Iwasaki, Y., Harada, A. (eds) Intracellular Delivery II. Fundamental Biomedical Technologies, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8896-0_4

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