Stimuli-responsive Carriers for Controlled Intracellular Drug Release

Author(s): Yan Sheng*, Jiaming Hu, Junfeng Shi, Ly James Lee.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 13 , 2019

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Background: Stimuli-responsive carriers are a class of drug delivery systems which can change their physicochemical properties and/or structural conformations in response to specific stimuli. Although passive and active drug targeting has proved to reduce the side effects to normal cells, controlled intracellular drug release should be included in drug carriers to enhance the bioavailability of drugs at the disease site.

Methods: This review focuses on several recent advances in the development of stimuli-responsive carriers for spatially and temporally controlled release of therapeutic agents in response to intracellular stimuli, such as pH, redox potential, reactive oxygen species, enzyme and temperature.

Results: Among the different types of stimuli, pH-responsive carriers have been mostly used to design intracellular controlled release system. The sharp difference of redox potential between inside and outside cells is attributed to the high variation in concentration of glutathione. ROS-responsive carriers are gaining much attention for selective release of therapeutic agents by sensing oxidative conditions at different levels. The advantages of utilizing enzymes as the trigger of stimuli-responsive carriers include diverse types of enzymes, high selectivity of enzyme catalyzed reactions and the mild reaction conditions involved. Abnormal temperature is another unique stimulus and has been widely used to trigger controlled release of drug in tumor cells.

Conclusion: Recent developments highlighted in this paper demonstrate that stimuli-responsive carriers possess great potential as a new platform for controlled intracellular drug release.

Keywords: Stimuli-responsive carriers, intracellular drug release, pH redox potential, reactive oxygen species, enzyme, temperature.

Yang, T.; Cui, F.D.; Choi, M.K.; Cho, J.W.; Chung, S.J.; Shim, C.K.; Kim, D.D. Enhanced solubility and stability of PEGylated liposomal paclitaxel: in vitro and in vivo evaluation. Int. J. Pharm., 2007, 338(1-2), 317-326. []. [PMID: 17368984].
Sheng, Y.; Chang, L.; Kuang, T.; Hu, J. PEG/heparin-decorated lipid-polymer hybrid nanoparticles for long-circulating drug delivery. RSC Advances, 2016, 6(28), 23279-23287. [].
Li, W.; Huang, L.; Ying, X.; Jian, Y.; Hong, Y.; Hu, F.; Du, Y. Antitumor drug delivery modulated by a polymeric micelle with an upper critical solution temperature. Angew. Chem. Int. Ed. Engl., 2015, 54(10), 3126-3131. []. [PMID: 25630768].
Cheng, X.; Jin, Y.; Sun, T.; Qi, R.; Li, H.; Fan, W. An injectable, dual pH and oxidation-responsive supramolecular hydrogel for controlled dual drug delivery. Colloids Surf. B Biointerfaces, 2016, 141, 44-52. []. [PMID: 26851440].
Lee, S.J.; Jeong, Y.I.; Park, H.K.; Kang, D.H.; Oh, J.S.; Lee, S.G.; Lee, H.C. Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery. Int. J. Nanomedicine, 2015, 10, 5489-5503. [PMID: 26357473].
Kuang, T.R.; Mi, H.Y.; Fu, D.J.; Jing, X.; Chen, B.Y.; Mou, W.J.; Peng, X.F. Fabrication of poly(lactic acid)/graphene oxide foams with highly oriented and elongated cell structure via unidirectional foaming using supercritical carbon dioxide. Ind. Eng. Chem. Res., 2015, 54(2), 758-768. [].
Kang, C.; Sun, Y.; Zhu, J.; Li, W.; Zhang, A.; Kuang, T.; Xie, J.; Yang, Z. Delivery of nanoparticles for treatment of brain tumor. Curr. Drug Metab., 2016, 17(8), 745-754. []. [PMID: 27469219].
Wang, H.; Xie, H.; Wu, J.; Wei, X.; Zhou, L.; Xu, X.; Zheng, S. Structure-based rational design of prodrugs to enable their combination with polymeric nanoparticle delivery platforms for enhanced antitumor efficacy. Angew. Chem. Int. Ed. Engl., 2014, 53(43), 11532-11537. []. [PMID: 25196427].
Wang, H.X.; Xie, H.Y.; Wang, J.G.; Wu, J.P.; Ma, X.J.; Li, L.L.; Wei, X.Y.; Ling, Q.; Song, P.H.; Zhou, L.; Xu, X.; Zheng, S.S. Self-assembling prodrugs by precise programming of molecular structures that contribute distinct stability, pharmacokinetics, and antitumor efficacy. Adv. Funct. Mater., 2015, 25(31), 4956-4965. [].
Kuang, T.R.; Fu, D.J.; Chang, L.Q.; Yang, Z.G.; Chen, Z.; Jin, L.L.; Chen, F.; Peng, X.F. recent progress in dendrimer-based gene delivery systems. Curr. Org. Chem., 2016, 20(17), 1820-1826. [].
Roberts, S.A. Drug metabolism and pharmacokinetics in drug discovery. Curr. Opin. Drug Discov. Devel., 2003, 6(1), 66-80. [PMID: 12613278].
Oh, Y.K.; Park, T.G. siRNA delivery systems for cancer treatment. Adv. Drug Deliv. Rev., 2009, 61(10), 850-862. []. [PMID: 19422869].
Xiao, H.; Fan, Y.; Liu, S.; Chen, X.; Huang, Y.; Jing, X. New polymer-platinum (II) antitumor conjugates. J. Control. Release, 2011, 152(Suppl. 1), e103-e104. []. [PMID: 22195780].
Xiao, H.; Song, H.; Yang, Q.; Cai, H.; Qi, R.; Yan, L.; Liu, S.; Zheng, Y.; Huang, Y.; Liu, T.; Jing, X. A prodrug strategy to deliver cisplatin(IV) and paclitaxel in nanomicelles to improve efficacy and tolerance. Biomaterials, 2012, 33(27), 6507-6519. []. [PMID: 22727463].
Xiao, H.; Qi, R.; Liu, S.; Hu, X.; Duan, T.; Zheng, Y.; Huang, Y.; Jing, X. Biodegradable polymer - cisplatin(IV) conjugate as a pro-drug of cisplatin(II). Biomaterials, 2011, 32(30), 7732-7739. []. [PMID: 21783244].
Sheng, Y.; Liu, C.; Yuan, Y.; Tao, X.; Yang, F.; Shan, X.; Zhou, H.; Xu, F. Long-circulating polymeric nanoparticles bearing a combinatorial coating of PEG and water-soluble chitosan. Biomaterials, 2009, 30(12), 2340-2348. []. [PMID: 19150737].
Yu, Z.; Cai, Z.; Chen, Q.; Liu, M.; Ye, L.; Ren, J.; Liao, W.; Liu, S. Engineering β-sheet peptide assemblies for biomedical applications. Biomater. Sci., 2016, 4(3), 365-374. []. [PMID: 26700207].
Yu, Z.; Xu, Q.; Dong, C.; Lee, S.S.; Gao, L.; Li, Y.; D’Ortenzio, M.; Wu, J. Self-assembling peptide nanofibrous hydrogel as a versatile drug delivery platform. Curr. Pharm. Des., 2015, 21(29), 4342-4354. []. [PMID: 26323419].
Yu, Z.; Schmaltz, R.M.; Bozeman, T.C.; Paul, R.; Rishel, M.J.; Tsosie, K.S.; Hecht, S.M. Selective tumor cell targeting by the disaccharide moiety of bleomycin. J. Am. Chem. Soc., 2013, 135(8), 2883-2886. []. [PMID: 23379863].
Yu, Z.; Paul, R.; Bhattacharya, C.; Bozeman, T.C.; Rishel, M.J.; Hecht, S.M. Structural features facilitating tumor cell targeting and internalization by bleomycin and its disaccharide. Biochemistry, 2015, 54(19), 3100-3109. []. [PMID: 25905565].
Petros, R.A.; DeSimone, J.M. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov., 2010, 9(8), 615-627. []. [PMID: 20616808].
Caliceti, P.; Veronese, F.M. Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv. Drug Deliv. Rev., 2003, 55(10), 1261-1277. []. [PMID: 14499706].
Owens, D.E., III; Peppas, N.A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm., 2006, 307(1), 93-102. []. [PMID: 16303268].
Kuang, T.R.; Liu, Y.R.; Gong, T.T.; Peng, X.F.; Hu, X.L.; Yu, Z.Q. Enzyme-responsive Nanoparticles for Anticancer Drug Delivery. Curr. Nanosci., 2016, 12(1), 38-46. [].
Torchilin, V.P. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J., 2007, 9(2), E128-E147. []. [PMID: 17614355].
Ganta, S.; Devalapally, H.; Shahiwala, A.; Amiji, M. A review of stimuli-responsive nanocarriers for drug and gene delivery. J. Control. Release, 2008, 126(3), 187-204. []. [PMID: 18261822].
Onaca, O.; Enea, R.; Hughes, D.W.; Meier, W. Stimuli responsive polymersomes as nanocarriers for drug and gene delivery. Macromol. Biosci., 2009, 9(2), 129-139. []. [PMID: 19107717].
Ke, C-J.; Lin, Y-J.; Hua, Y-C.; Chiang, W-L.; Chen, K-J.; Yang, W-C.; Liu, H-L.; Fu, C-C.; Sung, H-W. Multidrug release based on microneedle arrays filled with pH-responsive PLGA hollow microspheres. Biomaterials, 2012, 33(20), 5156-5165.
Urano, Y.; Asanuma, D.; Hama, Y.; Koyama, Y.; Barrett, T.; Kamiya, M.; Nagano, T.; Watanabe, T.; Hasegawa, A.; Choyke, P.L.; Kobayashi, H. Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes. Nat. Med., 2009, 15(1), 104-109. []. [PMID: 19029979].
Glunde, K.; Guggino, S.E.; Solaiyappan, M.; Pathak, A.P.; Ichikawa, Y.; Bhujwalla, Z.M. Extracellular acidification alters lysosomal trafficking in human breast cancer cells. Neoplasia, 2003, 5(6), 533-545. []. [PMID: 14965446].
Kuang, T.; Chang, L.; Peng, X.; Hu, X.; Gallego-Perez, D. Molecular beacon nano-sensors for probing living cancer cells. Trends Biotechnol., 2016. [PMID: 27692896].
Saito, G.; Swanson, J.A.; Lee, K-D. Drug delivery strategy utilizing conjugation via reversible disulfide linkages: Role and site of cellular reducing activities. Adv. Drug Deliv. Rev., 2003, 55(2), 199-215. []. [PMID: 12564977].
Block, M.L.; Zecca, L.; Hong, J.S. Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms. Nat. Rev. Neurosci., 2007, 8(1), 57-69. []. [PMID: 17180163].
Meyer, D.E.; Shin, B.C.; Kong, G.A.; Dewhirst, M.W.; Chilkoti, A. Drug targeting using thermally responsive polymers and local hyperthermia. J. Control. Release, 2001, 74(1-3), 213-224. []. [PMID: 11489497].
Matsuyama, S.; Llopis, J.; Deveraux, Q.L.; Tsien, R.Y.; Reed, J.C. Changes in intramitochondrial and cytosolic pH: Early events that modulate caspase activation during apoptosis. Nat. Cell Biol., 2000, 2(6), 318-325. []. [PMID: 10854321].
Casey, J.R.; Grinstein, S.; Orlowski, J. Sensors and regulators of intracellular pH. Nat. Rev. Mol. Cell Biol., 2010, 11(1), 50-61. []. [PMID: 19997129].
Chen, F.; Jiang, X.P.; Kuang, T.R.; Chang, L.Q.; Fu, D.J.; Yang, J.T.; Fan, P.; Zhong, M.Q. Polyelectrolyte/mesoporous silica hybrid materials for the high performance multiple-detection of pH value and temperature. Polym. Chem., 2015, 6(18), 3529-3536. [].
Bae, Y.; Nishiyama, N.; Fukushima, S.; Koyama, H.; Yasuhiro, M.; Kataoka, K. Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. Bioconjug. Chem., 2005, 16(1), 122-130. []. [PMID: 15656583].
Gillies, E.R.; Fréchet, J.M. pH-Responsive copolymer assemblies for controlled release of doxorubicin. Bioconjug. Chem., 2005, 16(2), 361-368. []. [PMID: 15769090].
Lee, S.J.; Min, K.H.; Lee, H.J.; Koo, A.N.; Rim, H.P.; Jeon, B.J.; Jeong, S.Y.; Heo, J.S.; Lee, S.C. Ketal cross-linked poly(ethylene glycol)-poly(amino acid)s copolymer micelles for efficient intracellular delivery of doxorubicin. Biomacromolecules, 2011, 12(4), 1224-1233. []. [PMID: 21344942].
Masson, C.; Garinot, M.; Mignet, N.; Wetzer, B.; Mailhe, P.; Scherman, D.; Bessodes, M. pH-sensitive PEG lipids containing orthoester linkers: New potential tools for nonviral gene delivery. J. Control. Release, 2004, 99(3), 423-434. []. [PMID: 15451600].
Xu, Z.; Gu, W.; Chen, L.; Gao, Y.; Zhang, Z.; Li, Y. A smart nanoassembly consisting of acid-labile vinyl ether PEG-DOPE and protamine for gene delivery: Preparation and in vitro transfection. Biomacromolecules, 2008, 9(11), 3119-3126. []. [PMID: 18834174].
Oishi, M.; Nagasaki, Y.; Itaka, K.; Nishiyama, N.; Kataoka, K. 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., 2005, 127(6), 1624-1625. []. [PMID: 15700981].
Lee, Y.; Fukushima, S.; Bae, Y.; Hiki, S.; Ishii, T.; Kataoka, K. A protein nanocarrier from charge-conversion polymer in response to endosomal pH. J. Am. Chem. Soc., 2007, 129(17), 5362-5363. []. [PMID: 17408272].
Parrott, M.C.; Luft, J.C.; Byrne, J.D.; Fain, J.H.; Napier, M.E.; Desimone, J.M. Tunable bifunctional silyl ether cross-linkers for the design of acid-sensitive biomaterials. J. Am. Chem. Soc., 2010, 132(50), 17928-17932. []. [PMID: 21105720].
Ke, C.J.; Su, T.Y.; Chen, H.L.; Liu, H.L.; Chiang, W.L.; Chu, P.C.; Xia, Y.; Sung, H.W. Smart multifunctional hollow microspheres for the quick release of drugs in intracellular lysosomal compartments. Angew. Chem. Int. Ed. Engl., 2011, 50(35), 8086-8089. []. [PMID: 21751316].
Ke, C.J.; Chiang, W.L.; Liao, Z.X.; Chen, H.L.; Lai, P.S.; Sun, J.S.; Sung, H.W. Real-time visualization of pH-responsive PLGA hollow particles containing a gas-generating agent targeted for acidic organelles for overcoming multi-drug resistance. Biomaterials, 2013, 34(1), 1-10. []. [PMID: 23044041].
Liu, J.; Ma, H.; Wei, T.; Liang, X.J. CO2 gas induced drug release from pH-sensitive liposome to circumvent doxorubicin resistant cells. Chem. Commun. (Camb.), 2012, 48(40), 4869-4871. []. [PMID: 22498879].
Chung, M.F.; Chen, K.J.; Liang, H.F.; Liao, Z.X.; Chia, W.T.; Xia, Y.; Sung, H.W. A liposomal system capable of generating CO2 bubbles to induce transient cavitation, lysosomal rupturing, and cell necrosis. Angew. Chem. Int. Ed. Engl., 2012, 51(40), 10089-10093. []. [PMID: 22952023].
Schafer, F.Q.; Buettner, G.R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic. Biol. Med., 2001, 30(11), 1191-1212. []. [PMID: 11368918].
Balendiran, G.K.; Dabur, R.; Fraser, D. The role of glutathione in cancer. Cell Biochem. Funct., 2004, 22(6), 343-352. []. [PMID: 15386533].
Sun, H.; Guo, B.; Cheng, R.; Meng, F.; Liu, H.; Zhong, Z. Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin. Biomaterials, 2009, 30(31), 6358-6366. []. [PMID: 19666191].
Wang, Y.C.; Wang, F.; Sun, T.M.; Wang, J. Redox-responsive nanoparticles from the single disulfide bond-bridged block copolymer as drug carriers for overcoming multidrug resistance in cancer cells. Bioconjug. Chem., 2011, 22(10), 1939-1945. []. [PMID: 21866903].
Chen, H.; Wang, Z.; Zong, S.; Wu, L.; Chen, P.; Zhu, D.; Wang, C.; Xu, S.; Cui, Y. SERS-fluorescence monitored drug release of a redox-responsive nanocarrier based on graphene oxide in tumor cells. ACS Appl. Mater. Interfaces, 2014, 6(20), 17526-17533. []. [PMID: 25272041].
Yu, C.; Qian, L.; Ge, J.; Fu, J.; Yuan, P.; Yao, S.C.; Yao, S.Q. Cell-Penetrating Poly(disulfide) assisted intracellular delivery of mesoporous silica nanoparticles for inhibition of miR-21 function and detection of subsequent therapeutic effects. Angew. Chem. Int. Ed. Engl., 2016, 55(32), 9272-9276. []. [PMID: 27325284].
Xiao, H.; Noble, G.T.; Stefanick, J.F.; Qi, R.; Kiziltepe, T.; Jing, X.; Bilgicer, B. Photosensitive Pt(IV)-azide prodrug-loaded nanoparticles exhibit controlled drug release and enhanced efficacy in vivo. J. Control. Release, 2014, 173, 11-17. []. [PMID: 24511610].
Ma, P.A.; Xiao, H.H.; Li, C.X.; Dai, Y.L.; Cheng, Z.Y.; Hou, Z.Y.; Lin, J. Inorganic nanocarriers for platinum drug delivery. Mater. Today, 2015, 18(10), 554-564. [].
Wang, Y.C.; Wang, F.; Sun, T.M.; Wang, J. Redox-responsive nanoparticles from the single disulfide bond-bridged block copolymer as drug carriers for overcoming multidrug resistance in cancer cells. Bioconjug. Chem., 2011, 22(10), 1939-1945. []. [PMID: 21866903].
Hu, Y.W.; Du, Y.Z.; Liu, N.; Liu, X.; Meng, T.T.; Cheng, B.L.; He, J.B.; You, J.; Yuan, H.; Hu, F.Q. Selective redox-responsive drug release in tumor cells mediated by chitosan based glycolipid-like nanocarrier. J. Control. Release, 2015, 206, 91-100. []. [PMID: 25796347].
Winterbourn, C.C. Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol., 2008, 4(5), 278-286. []. [PMID: 18421291].
Yu, B.P. Cellular defenses against damage from reactive oxygen species. Physiol. Rev., 1994, 74(1), 139-162. []. [PMID: 8295932].
Napoli, A.; Valentini, M.; Tirelli, N.; Müller, M.; Hubbell, J.A. Oxidation-responsive polymeric vesicles. Nat. Mater., 2004, 3(3), 183-189. []. [PMID: 14991021].
Mahmoud, E.A.; Sankaranarayanan, J.; Morachis, J.M.; Kim, G.; Almutairi, A. Inflammation responsive logic gate nanoparticles for the delivery of proteins. Bioconjug. Chem., 2011, 22(7), 1416-1421. []. [PMID: 21688843].
Wei, J.; Cheang, T.; Tang, B.; Xia, H.; Xing, Z.; Chen, Z.; Fang, Y.; Chen, W.; Xu, A.; Wang, S.; Luo, J. The inhibition of human bladder cancer growth by calcium carbonate/CaIP6 nanocomposite particles delivering AIB1 siRNA. Biomaterials, 2013, 34(4), 1246-1254. []. [PMID: 23127333].
Wilson, D.S.; Dalmasso, G.; Wang, L.; Sitaraman, S.V.; Merlin, D.; Murthy, N. Orally delivered thioketal nanoparticles loaded with TNF-α-siRNA target inflammation and inhibit gene expression in the intestines. Nat. Mater., 2010, 9(11), 923-928. []. [PMID: 20935658].
Chiang, J.K.; Sung, M.L.; Yu, H.R.; Chang, H.I.; Kuo, H.C.; Tsai, T.C.; Yen, C.K.; Chen, C.N. Homocysteine induces smooth muscle cell proliferation through differential regulation of cyclins A and D1 expression. J. Cell. Physiol., 2011, 226(4), 1017-1026. []. [PMID: 20857402].
Broaders, K.E.; Grandhe, S.; Fréchet, J.M. A biocompatible oxidation-triggered carrier polymer with potential in therapeutics. J. Am. Chem. Soc., 2011, 133(4), 756-758. []. [PMID: 21171594].
Deng, H.; Zhao, X.; Liu, J.; Deng, L.; Zhang, J.; Liu, J.; Dong, A. Reactive oxygen species (ROS) responsive PEG-PCL nanoparticles with pH-controlled negative-to-positive charge reversal for intracellular delivery of doxorubicin. J. Mater. Chem. B Mater. Biol. Med., 2015, 3(48), 9397-9408. [].
Shim, M.S.; Xia, Y. A reactive oxygen species (ROS)-responsive polymer for safe, efficient, and targeted gene delivery in cancer cells. Angew. Chem. Int. Ed. Engl., 2013, 52(27), 6926-6929. []. [PMID: 23716349].
Zhang, D.; Wei, Y.; Chen, K.; Zhang, X.; Xu, X.; Shi, Q.; Han, S.; Chen, X.; Gong, H.; Li, X.; Zhang, J. Biocompatible reactive oxygen species (ROS)-responsive nanoparticles as superior drug delivery vehicles. Adv. Healthc. Mater., 2015, 4(1), 69-76. []. [PMID: 25147049].
Gupta, M.K.; Meyer, T.A.; Nelson, C.E.; Duvall, C.L. Poly(PS-b-DMA) micelles for reactive oxygen species triggered drug release. J. Control. Release, 2012, 162(3), 591-598. []. [PMID: 22889714].
Deryugina, E.I.; Quigley, J.P. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev., 2006, 25(1), 9-34. []. [PMID: 16680569].
Nelson, A.R.; Fingleton, B.; Rothenberg, M.L.; Matrisian, L.M. Matrix metalloproteinases: biologic activity and clinical implications. J. Clin. Oncol., 2000, 18(5), 1135-1149. []. [PMID: 10694567].
Andresen, T.L.; Thompson, D.H.; Kaasgaard, T. Enzyme-triggered nanomedicine: Drug release strategies in cancer therapy. Mol. Membr. Biol., 2010, 27(7), 353-363. []. [PMID: 20939771].
Chang, L.; Gallego-Perez, D.; Chiang, C.L.; Bertani, P.; Kuang, T.; Sheng, Y.; Chen, F.; Chen, Z.; Shi, J.; Yang, H.; Huang, X.; Malkoc, V.; Lu, W.; Lee, L.J. Controllable large-scale transfection of primary mammalian cardiomyocytes on a nanochannel array platform. Small, 2016, 12(43), 5971-5980. []. [PMID: 27648733].
Wang, Y.; Shim, M.S.; Levinson, N.S.; Sung, H.W.; Xia, Y. Stimuli-responsive materials for controlled release of theranostic agents. Adv. Funct. Mater., 2014, 24(27), 4206-4220.
Duxbury, C.J.; Hilker, I.; de Wildeman, S.M.; Heise, A. Enzyme-responsive materials: Chirality to program polymer reactivity. Angew. Chem. Int. Ed. Engl., 2007, 46(44), 8452-8454. []. [PMID: 17918272].
Park, C.; Kim, H.; Kim, S.; Kim, C. Enzyme responsive nanocontainers with cyclodextrin gatekeepers and synergistic effects in release of guests. J. Am. Chem. Soc., 2009, 131(46), 16614-16615. []. [PMID: 19919132].
Tanaka, K.; Kitamura, N.; Chujo, Y. Biodegradable main-chain phosphate-caged fluorescein polymers for the evaluation of enzymatic activity. Macromolecules, 2010, 43(14), 6180-6184. [].
Lee, S.J.; Jeong, Y.I.; Park, H.K.; Kang, D.H.; Oh, J.S.; Lee, S.G.; Lee, H.C. Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery. Int. J. Nanomedicine, 2015, 10, 5489-5503. [PMID: 26357473].
Fukumura, D.; Jain, R.K. Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J. Cell. Biochem., 2007, 101(4), 937-949. []. [PMID: 17171643].
de Las Heras Alarcon, C.; Pennadam, S.; Alexander, C. Stimuli responsive polymers for biomedical applications. Chem. Soc. Rev., 2005, 34(3), 276-285. []. [PMID: 15726163].
Wang, Y.C.; Tang, L.Y.; Li, Y.; Wang, J. Thermoresponsive block copolymers of poly(ethylene glycol) and polyphosphoester: thermo-induced self-assembly, biocompatibility, and hydrolytic degradation. Biomacromolecules, 2009, 10(1), 66-73. []. [PMID: 19133835].
Wang, Y.C.; Yuan, Y.Y.; Du, J.Z.; Yang, X.Z.; Wang, J. Recent progress in polyphosphoesters: from controlled synthesis to biomedical applications. Macromol. Biosci., 2009, 9(12), 1154-1164. []. [PMID: 19924681].
Chun, C.; Lee, S.M.; Kim, S.Y.; Yang, H.K.; Song, S.C. Thermosensitive poly(organophosphazene)-paclitaxel conjugate gels for antitumor applications. Biomaterials, 2009, 30(12), 2349-2360. []. [PMID: 19178941].
Lee, B.H.; Lee, Y.M.; Sohn, Y.S.; Song, S-C. A thermosensitive poly (organophosphazene) gel. Macromolecules, 2002, 35(10), 3876-3879. [].
Chun, C.; Lee, S.M.; Kim, S.Y.; Yang, H.K.; Song, S-C. Thermosensitive poly (organophosphazene) paclitaxel conjugate gels for antitumor applications. Biomaterials, 2009, 30(12), 2349-2360. []. [PMID: 19178941].
Chiappetta, D.A.; Sosnik, A. Poly(ethylene oxide)-poly(propylene oxide) block copolymer micelles as drug delivery agents: improved hydrosolubility, stability and bioavailability of drugs. Eur. J. Pharm. Biopharm., 2007, 66(3), 303-317. []. [PMID: 17481869].
Dumortier, G.; Grossiord, J.L.; Agnely, F.; Chaumeil, J.C. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm. Res., 2006, 23(12), 2709-2728. []. [PMID: 17096184].
Ron, E.S.; Bromberg, L.E. Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. Adv. Drug Deliv. Rev., 1998, 31(3), 197-221. []. [PMID: 10837626].
Ron, E.S.; Bromberg, L.E. Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. Adv. Drug Deliv. Rev., 1998, 31(3), 197-221. []. [PMID: 10837626].
Gil, E.S.; Hudson, S.M. Stimuli-responsive polymers and their bioconjugates. Prog. Polym. Sci., 2004, 29(12), 1173-1222. [].
Schild, H.G. Poly (N-isopropylacrylamide): experiment, theory and application. Prog. Polym. Sci., 1992, 17(2), 163-249. [].
Hwang, M.J.; Suh, J.M.; Bae, Y.H.; Kim, S.W.; Jeong, B. Caprolactonic poloxamer analog: PEG-PCL-PEG. Biomacromolecules, 2005, 6(2), 885-890.
Jeong, B.; Kibbey, M.R.; Birnbaum, J.C.; Won, Y-Y.; Gutowska, A. Thermogelling biodegradable polymers with hydrophilic backbones: PEG-g-PLGA. Macromolecules, 2000, 33(22), 8317-8322. [].
Chiang, W-H.; Huang, W-C.; Chang, Y-J.; Shen, M-Y.; Chen, H-H.; Chern, C-S.; Chiu, H-C. Doxorubicin-loaded nanogel assemblies with pH/thermo-triggered payload release for intracellular drug delivery. Macromol. Chem. Phys., 2014, 215(13), 1332-1341. [].
Qin, Y.; Chen, J.; Bi, Y.; Xu, X.; Zhou, H.; Gao, J.; Hu, Y.; Zhao, Y.; Chai, Z. Near-infrared light remote-controlled intracellular anti-cancer drug delivery using thermo/pH sensitive nanovehicle. Acta Biomater., 2015, 17, 201-209. []. [PMID: 25644449].
Holzapfel, B.M.; Reichert, J.C.; Schantz, J-T.; Gbureck, U.; Rackwitz, L.; Nöth, U.; Jakob, F.; Rudert, M.; Groll, J.; Hutmacher, D.W. How smart do biomaterials need to be? A translational science and clinical point of view. Adv. Drug Deliv. Rev., 2013, 65(4), 581-603. []. [PMID: 22820527].

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Year: 2019
Page: [2377 - 2388]
Pages: 12
DOI: 10.2174/0929867324666170830102409
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