Stimuli-responsive nanocarriers for drug delivery
Source abstract
Abstract
Spurred by recent progress in materials chemistry and drug delivery, stimuli-responsive devices that deliver a drug in spatial-, temporal- and dosage-controlled fashions have become possible. Implementation of such devices requires the use of biocompatible materials that are susceptible to a specific physical incitement or that, in response to a specific stimulus, undergo a protonation, a hydrolytic cleavage or a (supra)molecular conformational change. In this Review, we discuss recent advances in the design of nanoscale stimuli-responsive systems that are able to control drug biodistribution in response to specific stimuli, either exogenous (variations in temperature, magnetic field, ultrasound intensity, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients).
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · Advanced Drug Delivery Systems · Graphene and Nanomaterials Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
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1. Yatvin, M. B., Weinstein, J. N., Dennis, W. H. & Blumenthal, R. Design of liposomes for enhanced local release of drugs by hyperthermia. Science 202, 1290–1293 (1978).10.1126/science.364652 ↗
2. Tagami, T. et al. MRI monitoring of intratumoral drug delivery and prediction of the therapeutic effect with a multifunctional thermosensitive liposome. Biomaterials 32, 6570–6578 (2011).10.1016/j.biomaterials.2011.05.029 ↗
3. Al-Ahmady, Z. S. et al. Lipid–peptide vesicle nanoscale hybrids for triggered drug release by mild hyperthermia in vitro and in vivo. ACS Nano 6, 9335–9346 (2012).10.1021/nn302148p ↗
4. Chen, K-J. et al. A thermoresponsive bubble-generating liposomal system for triggering localized extracellular drug delivery. ACS Nano 7, 438–446 (2013).10.1021/nn304474j ↗
5. Smith, B. et al. Hyperthermia-triggered intracellular delivery of anticancer agent to HER2+ cells by HER2-specific affibody (ZHER2-GS-Cys)-conjugated thermosensitive liposomes (HER2+ affisomes). J. Control. Release 153, 187–194 (2011).10.1016/j.jconrel.2011.04.005 ↗
6. Zhang, J., Chen, H., Xu, L. & Gu, Y. The targeted behavior of thermally responsive nanohydrogel evaluated by NIR system in mouse model. J. Control. Release 131, 34–40 (2008).10.1016/j.jconrel.2008.07.019 ↗
7. Cheng, Y. et al. Thermally controlled release of anticancer drug from self-assembled γ-substituted amphiphilic poly(ε-caprolactone) micellar nanoparticles. Biomacromolecules 13, 2163–2173 (2012).10.1021/bm300823y ↗
8. MacEwan, S. R. & Chilkoti, A. Digital switching of local arginine density in a genetically encoded self-assembled polypeptide nanoparticle controls cellular uptake. Nano Lett. 12, 3322–3328 (2012).10.1021/nl301529p ↗
9. Lee, S. H., Choi, S. H., Kim, S. H. & Park, T. G. Thermally sensitive cationic polymer nanocapsules for specific cytosolic delivery and efficient gene silencing of siRNA: swelling induced physical disruption of endosome by cold shock. J. Control. Release 125, 25–32 (2008).10.1016/j.jconrel.2007.09.011 ↗
10. Yang, H. W. et al. Self-protecting core–shell magnetic nanoparticles for targeted, traceable, long half-life delivery of BCNU to gliomas. Biomaterials 32, 6523–6532 (2011).10.1016/j.biomaterials.2011.05.047 ↗
11. Zhang, L. et al. General route to multifunctional uniform yolk/mesoporous silica shell nanocapsules: a platform for simultaneous cancer-targeted imaging and magnetically guided drug delivery. Chem. Eur. J. 18, 12512–12521 (2012).10.1002/chem.201200030 ↗
12. Hua, M-Y. et al. The effectiveness of a magnetic nanoparticle-based delivery system for BCNU in the treatment of gliomas. Biomaterials 32, 516–527 (2011).10.1016/j.biomaterials.2010.09.065 ↗
13. Plassat, V. et al. Anti-estrogen-loaded superparamagnetic liposomes for intracellular magnetic targeting and treatment of breast cancer tumors. Adv. Funct. Mater. 21, 83–92 (2011).10.1002/adfm.201001450 ↗
14. Zhang, F. et al. Mesoporous multifunctional upconversion luminescent and magnetic “nanorattle” materials for targeted chemotherapy. Nano Lett. 12, 61–67 (2012).10.1021/nl202949y ↗
15. Arias, J. L. et al. Squalene based nanocomposites: a new platform for the design of multifunctional pharmaceutical theragnostics. ACS Nano 5, 1513–1521 (2011).10.1021/nn1034197 ↗
16. Qin, J. et al. Injectable superparamagnetic ferrogels for controlled release of hydrophobic drugs. Adv. Mater. 21, 1354–1357 (2009).10.1002/adma.200800764 ↗
17. Cai, K. et al. Magnetically triggered reversible controlled drug delivery from microfabricated polymeric multireservoir devices. Adv. Mater. 21, 4045–4049 (2009).10.1002/adma.200900593 ↗
18. Park, J. W., Bae, K. H., Kim, C. & Park, T. G. Clustered magnetite nanocrystals cross-linked with PEI for efficient siRNA delivery. Biomacromolecules 12, 457–465 (2010).10.1021/bm101244j ↗
19. Prijic, S. et al. Surface modified magnetic nanoparticles for immuno-gene therapy of murine mammary adenocarcinoma. Biomaterials 33, 4379–4391 (2012).10.1016/j.biomaterials.2012.02.061 ↗
20. Jenkins, S. I., Pickard, M. R., Granger, N. & Chari, D. M. Magnetic nanoparticle-mediated gene transfer to oligodendrocyte precursor cell transplant populations is enhanced by magnetofection strategies. ACS Nano 5, 6527–6538 (2011).10.1021/nn2018717 ↗
21. Al-Deen, F. N., Ho, J., Selomulya, C., Ma, C. & Coppel, R. Superparamagnetic nanoparticles for effective delivery of malaria DNA vaccine. Langmuir 27, 3703–3712 (2011).10.1021/la104479c ↗
22. Tang, Y. S. et al. Bacterial magnetic particles as a novel and efficient gene vaccine delivery system. Gene Ther. 19, 1187–1195 (2012).10.1038/gt.2011.197 ↗
23. Sapet, C., Pellegrino, C., Laurent, N., Sicard, F. & Zelphati, O. Magnetic nanoparticles enhance adenovirus transduction in vitro and in vivo. Pharm. Res. 29, 1203–1218 (2012).10.1007/s11095-011-0629-9 ↗
24. Muthana, M. et al. A novel magnetic approach to enhance the efficacy of cell-based gene therapies. Gene Ther. 15, 902–910 (2008).10.1038/gt.2008.57 ↗
25. Chorny, M., Hood, E., Levy, R. J. & Muzykantov, V. R. Endothelial delivery of antioxidant enzymes loaded into non-polymeric magnetic nanoparticles. J. Control. Release 146, 144–151 (2010).10.1016/j.jconrel.2010.05.003 ↗
26. Huang, H. Y. et al. Self-assembling PVA-F127 thermosensitive nanocarriers with highly sensitive magnetically-triggered drug release for epilepsy therapy in vivo. J. Mater. Chem. 22, 8566–8573 (2012).10.1039/c2jm00032f ↗
27. Katagiri, K. et al. Magnetoresponsive on-demand release of hybrid liposomes formed from Fe3O4 nanoparticles and thermosensitive block copolymers. Small 7, 1683–1689 (2011).10.1002/smll.201002180 ↗
28. Satarkar, N. S. & Zach Hilt, J. Hydrogel nanocomposites as remote-controlled biomaterials. Acta Biomater. 4, 11–16 (2008).10.1016/j.actbio.2007.07.009 ↗
29. Hu, S-H., Chen, S-Y. & Gao, X. Multifunctional nanocapsules for simultaneous encapsulation of hydrophilic and hydrophobic compounds and on-demand release. ACS Nano 6, 2558–2565 (2012).10.1021/nn205023w ↗
30. Bringas, E. et al. Triggered release in lipid bilayer-capped mesoporous silica nanoparticles containing SPION using an alternating magnetic field. Chem. Commun. 48, 5647–5649 (2012).10.1039/c2cc31563g ↗
31. Hu, S-H., Liu, D-M., Tung, W-L., Liao, C-F. & Chen, S-Y. Surfactant-free, self-assembled PVA-iron oxide/silica core–shell nanocarriers for highly sensitive, magnetically controlled drug release and ultrahigh cancer cell uptake efficiency. Adv. Funct. Mater. 18, 2946–2955 (2008).10.1002/adfm.200800428 ↗
32. Hu, S-H., Chen, S-Y., Liu, D-M. & Hsiao, C-S. Core/single-crystal-shell nanospheres for controlled drug release via a magnetically triggered rupturing mechanism. Adv. Mater. 20, 2690–2695 (2008).10.1002/adma.200800193 ↗
33. Pradhan, P. et al. Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. J. Control. Release 142, 108–121 (2010).10.1016/j.jconrel.2009.10.002 ↗
34. Thomas, C. R. et al. Noninvasive remote-controlled release of drug molecules in vitro using magnetic actuation of mechanized nanoparticles. J. Am. Chem. Soc. 132, 10623–10625 (2010).10.1021/ja1022267 ↗
35. Hoare, T. et al. Magnetically triggered nanocomposite membranes: a versatile platform for triggered drug release. Nano Lett. 11, 1395–1400 (2011).10.1021/nl200494t ↗
36. Ruiz-Hernaández, E., Baeza, A. & Vallet-Regiá, M. Smart drug delivery through DNA/magnetic nanoparticle gates. ACS Nano 5, 1259–1266 (2011).10.1021/nn1029229 ↗
37. Derfus, A. M. et al. Remotely triggered release from magnetic nanoparticles. Adv. Mater. 19, 3932–3936 (2007).10.1002/adma.200700091 ↗
38. Stanley, S. A. et al. Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice. Science 336, 604–608 (2012).10.1126/science.1216753 ↗
39. Schroeder, A. et al. Ultrasound triggered release of cisplatin from liposomes in murine tumors. J. Control. Release 137, 63–68 (2009).10.1016/j.jconrel.2009.03.007 ↗
40. Kheirolomoom, A. et al. Copper-doxorubicin as a nanoparticle cargo retains efficacy with minimal toxicity. Mol. Pharm. 7, 1948–1958 (2010).10.1021/mp100245u ↗
41. Rapoport, N. Y., Kennedy, A. M., Shea, J. E., Scaife, C. L. & Nam, K. H. Controlled and targeted tumor chemotherapy by ultrasound-activated nanoemulsions/microbubbles. J. Control. Release 138, 268–276 (2009).10.1016/j.jconrel.2009.05.026 ↗
42. Wang, C. H. et al. Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis. Biomaterials 33, 1939–1947 (2012).10.1016/j.biomaterials.2011.11.036 ↗
43. Tran, M. A. et al. Targeting V600EB-Raf and Akt3 using nanoliposomal-small interfering RNA inhibits cutaneous melanocytic lesion development. Cancer Res. 68, 7638–7649 (2008).10.1158/0008-5472.CAN-07-6614 ↗
44. Javadi, M., Pitt, W. G., Belanp, D. M., Tsosie, N. H. & Hartley, J. M. Encapsulating nanoemulsions inside eliposomes for ultrasonic drug delivery. Langmuir 28, 14720–14729 (2012).10.1021/la303464v ↗
45. Britton, G. L. et al. In vivo therapeutic gas delivery for neuroprotection with echogenic liposomes. Circulation 122, 1578–1587 (2010).10.1161/CIRCULATIONAHA.109.879338 ↗
46. Negishi, Y. et al. Enhanced laminin-derived peptide AG73-mediated liposomal gene transfer by bubble liposomes and ultrasound. Mol. Pharm. 7, 217–226 (2010).10.1021/mp900214s ↗
47. Negishi, Y. et al. Systemic delivery systems of angiogenic gene by novel bubble liposomes containing cationic lipid and ultrasound exposure. Mol. Pharm. 9, 1834–1840 (2012).10.1021/mp200554c ↗
48. Un, K. et al. Suppression of melanoma growth and metastasis by DNA vaccination using an ultrasound-responsive and mannose-modified gene carrier. Mol. Pharm. 8, 543–554 (2011).10.1021/mp100369n ↗
49. Ranjan, A. et al. Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit V×2 tumor model. J. Control. Release 158, 487–494 (2012).10.1016/j.jconrel.2011.12.011 ↗
50. Lu, J., Choi, E., Tamanoi, F. & Zink, J. I. Light-activated nanoimpeller-controlled drug release in cancer cells. Small 4, 421–426 (2008).10.1002/smll.200700903 ↗
51. Yuan, Q. et al. Photon-manipulated drug release from a mesoporous nanocontainer controlled by azobenzene-modified nucleic acid. ACS Nano 6, 6337–6344 (2012).10.1021/nn3018365 ↗
52. Yan, H. et al. Functional mesoporous silica nanoparticles for photothermal-controlled drug delivery in vivo. Angew. Chem. Int. Ed. 51, 8373–8377 (2012).10.1002/anie.201203993 ↗
53. Liu, Y. C. et al. Photo-assisted gene delivery using light-responsive catanionic vesicles. Langmuir 25, 5713–5724 (2009).10.1021/la803588d ↗
54. Tong, R., Hemmati, H. D., Langer, R. & Kohane, D. S. Photoswitchable nanoparticles for triggered tissue penetration and drug delivery. J. Am. Chem. Soc. 134, 8848–8855 (2012).10.1021/ja211888a ↗
55. He, D., He, X., Wang, K., Cao, J. & Zhao, Y. A light-responsive reversible molecule-gated system using thymine-modified mesoporous silica nanoparticles. Langmuir 28, 4003–4008 (2012).10.1021/la2047504 ↗
56. Agasti, S. S. et al. Photoregulated release of caged anticancer drugs from gold nanoparticles. J. Am. Chem. Soc. 131, 5728–5729 (2009).10.1021/ja900591t ↗
57. Vivero-Escoto, J. L., Slowing, I. I., Wu, C-W. & Lin, V. S. Y. Photoinduced intracellular controlled release drug delivery in human cells by gold-capped mesoporous silica nanosphere. J. Am. Chem. Soc. 131, 3462–3463 (2009).10.1021/ja900025f ↗
58. Azagarsamy, M. A., Alge, D. L., Radhakrishnan, S. J., Tibbitt, M. W. & Anseth, K. S. Photocontrolled nanoparticles for on-demand release of proteins. Biomacromolecules 13, 2219–2224 (2012).10.1021/bm300646q ↗
59. Schroeder, A. et al. Remotely activated protein-producing nanoparticles. Nano Lett. 12, 2685–2689 (2012).10.1021/nl2036047 ↗
60. Yang, J. et al. Smart drug-loaded polymer gold nanoshells for systemic and localized therapy of human epithelial cancer. Adv. Mater. 21, 4339–4342 (2009).10.1002/adma.200900334 ↗
61. You, J. et al. Effective photothermal chemotherapy using doxorubicin-loaded gold nanospheres that target EphB4 receptors in tumors. Cancer Res. 72, 4777–4786 (2012).10.1158/0008-5472.CAN-12-1003 ↗
62. Xiao, Z. et al. DNA self-assembly of targeted near-infrared-responsive gold nanoparticles for cancer thermo-chemotherapy. Angew. Chem. Int. Ed. 54, 11853–11857 (2012).10.1002/anie.201204018 ↗
63. Chang, Y. T. et al. Near-infrared light-responsive intracellular drug and siRNA release using Au nanoensembles with oligonucleotide-capped silica shell. Adv. Mater. 24, 3309–3314 (2012).10.1002/adma.201200785 ↗
64. Lee, S. M. et al. Multifunctional nanoparticles for targeted chemophotothermal treatment of cancer cells. Angew. Chem. Int. Ed. 50, 7581–7586 (2011).10.1002/anie.201101783 ↗
65. Ma, Y. et al. Gold nanoshell nanomicelles for potential magnetic resonance imaging, light-triggered drug release, and photothermal therapy. Adv. Funct. Mater. 23, 815–822 (2012).10.1002/adfm.201201663 ↗
66. Yavuz, M. S. et al. Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nature Mater. 8, 935–939 (2009).10.1038/nmat2564 ↗
67. Agarwal, A., Mackey, M. A., El-Sayed, M. A. & Bellamkonda, R. V. Remote triggered release of doxorubicin in tumors by synergistic application of thermosensitive liposomes and gold nanorods. ACS Nano 5, 4919–4926 (2011).10.1021/nn201010q ↗
68. Lukianova-Hleb, E. Y., Belyanin, A., Kashinath, S., Wu, X. & Lapotko, D. O. Plasmonic nanobubble-enhanced endosomal escape processes for selective and guided intracellular delivery of chemotherapy to drug-resistant cancer cells. Biomaterials 33, 1821–1826 (2012).10.1016/j.biomaterials.2011.11.015 ↗
69. Ge, J., Neofytou, E., Cahill, T. J., Beygui, R. E. & Zare, R. N. Drug release from electric-field-responsive nanoparticles. ACS Nano 6, 227–233 (2011).10.1021/nn203430m ↗
70. Im, J. S., Bai, B. C. & Lee, Y-S. The effect of carbon nanotubes on drug delivery in an electro-sensitive transdermal drug delivery system. Biomaterials 31, 1414–1419 (2010).10.1016/j.biomaterials.2009.11.004 ↗
71. Liu, K-H., Liu, T-Y., Chen, S-Y. & Liu, D-M. Drug release behavior of chitosan–montmorillonite nanocomposite hydrogels following electrostimulation. Acta Biomater. 4, 1038–1045 (2008).10.1016/j.actbio.2008.01.012 ↗
72. Yan, Q. et al. Voltage-responsive vesicles based on orthogonal assembly of two homopolymers. J. Am. Chem. Soc. 132, 9268–9270 (2010).10.1021/ja1027502 ↗
73. Kim, H., Jeong, S-M. & Park, J-W. Electrical switching between vesicles and micelles via redox-responsive self-assembly of amphiphilic rod–coils. J. Am. Chem. Soc. 133, 5206–5209 (2011).10.1021/ja200297j ↗
74. Kim, J. A. & Lee, W. G. Role of weakly polarized nanoparticles in electroporation. Nanoscale 3, 1526–1532 (2011).10.1039/c0nr00448k ↗
75. Wang, S., Zhang, X., Yu, B., Lee, R. J. & Lee, L. J. Targeted nanoparticles enhanced flow electroporation of antisense oligonucleotides in leukemia cells. Biosens. Bioelectron. 26, 778–783 (2010).10.1016/j.bios.2010.06.025 ↗
76. Tomoda, K. et al. Enhanced transdermal permeability of estradiol using combination of PLGA nanoparticles system and iontophoresis. Colloids Surf. B 97, 84–89 (2012).10.1016/j.colsurfb.2012.04.002 ↗
77. Chen, H. et al. Iontophoresis-driven penetration of nanovesicles through microneedle-induced skin microchannels for enhancing transdermal delivery of insulin. J. Control. Release 139, 63–72 (2009).10.1016/j.jconrel.2009.05.031 ↗
78. Dohnert, M. B. et al. Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis. Int. J. Nanomed. 7, 1651–1657 (2012).10.2147/IJN.S25164 ↗
79. Chopra, P., Hao, J. & Li, S. K. Sustained release micellar carrier systems for iontophoretic transport of dexamethasone across human sclera. J. Control. Release 160, 96–104 (2012).10.1016/j.jconrel.2012.01.032 ↗
80. Deng, Z. et al. Hollow chitosan–silica nanospheres as pH-sensitive targeted delivery carriers in breast cancer therapy. Biomaterials 32, 4976–4986 (2011).10.1016/j.biomaterials.2011.03.050 ↗
81. Min, K. H. et al. Tumoral acidic pH-responsive MPEG-poly(β-amino ester) polymeric micelles for cancer targeting therapy. J. Control. Release 144, 259–266 (2010).10.1016/j.jconrel.2010.02.024 ↗
82. Gao, G. H. et al. The use of pH-sensitive positively charged polymeric micelles for protein delivery. Biomaterials 33, 9157–9164 (2012).10.1016/j.biomaterials.2012.09.016 ↗
83. Lee, E. S. et al. Super pH-sensitive multifunctional polymeric micelle for tumor pHe specific TAT exposure and multidrug resistance. J. Control. Release 129, 228–236 (2008).10.1016/j.jconrel.2008.04.024 ↗
84. Koren, E., Apte, A., Jani, A. & Torchilin, V. P. Multifunctional PEGylated 2C5-immunoliposomes containing pH-sensitive bonds and TAT peptide for enhanced tumor cell internalization and cytotoxicity. J. Control. Release 160, 264–273 (2012).10.1016/j.jconrel.2011.12.002 ↗
85. Quan, C-Y. et al. Core–shell nanosized assemblies mediated by the α–β cyclodextrin dimer with a tumor-triggered targeting property. ACS Nano 4, 4211–4219 (2010).10.1021/nn100534q ↗
86. Karve, S., Bandekar, A., Ali, M. R. & Sofou, S. The pH-dependent association with cancer cells of tunable functionalized lipid vesicles with encapsulated doxorubicin for high cell-kill selectivity. Biomaterials 31, 4409–4416 (2010).10.1016/j.biomaterials.2010.01.064 ↗
87. Du, J-Z., Du, X-J., Mao, C-Q. & Wang, J. Tailor-made dual pH-sensitive polymer–doxorubicin nanoparticles for efficient anticancer drug delivery. J. Am. Chem. Soc. 133, 17560–17563 (2011).10.1021/ja207150n ↗
88. Radovic-Moreno, A. F. et al. Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics. ACS Nano 6, 4279–4287 (2012).10.1021/nn3008383 ↗
89. Wang, X-Q. & Zhang, Q. pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs. Eur. J. Pharm. Biopharm. 82, 219–229 (2012).10.1016/j.ejpb.2012.07.014 ↗
90. Qu, W. et al. A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1. Int. J. Nanomed. 7, 4983–4994 (2012).
91. Yang, Y. Q., Zheng, L. S., Guo, X. D., Qian, Y. & Zhang, L. J. pH-sensitive micelles self-assembled from amphiphilic copolymer brush for delivery of poorly water-soluble drugs. Biomacromolecules 12, 116–122 (2010).10.1021/bm101058w ↗
92. Lee, C-H., Lo, L-W., Mou, C-Y. & Yang, C-S. Synthesis and characterization of positive-charge functionalized mesoporous silica nanoparticles for oral drug delivery of an anti-inflammatory drug. Adv. Funct. Mater. 18, 3283–3292 (2008).10.1002/adfm.200800521 ↗
93. Sung, H. W., Sonaje, K., Liao, Z. X., Hsu, L. W. & Chuang, E. Y. pH-responsive nanoparticles shelled with chitosan for oral delivery of insulin: from mechanism to therapeutic applications. Acc. Chem. Res. 45, 619–629 (2012).10.1021/ar200234q ↗
94. Griset, A. P. et al. Expansile nanoparticles: synthesis, characterization, and in vivo efficacy of an acid-responsive polymeric drug delivery system. J. Am. Chem. Soc. 131, 2469–2471 (2009).10.1021/ja807416t ↗
95. You, J-O. & Auguste, D. T. Nanocarrier cross-linking density and pH sensitivity regulate intracellular gene transfer. Nano Lett. 9, 4467–4473 (2009).10.1021/nl902789s ↗
96. Zhu, S., Lansakara-P, D. S. P., Li, X. & Cui, Z. Lysosomal delivery of a lipophilic gemcitabine prodrug using novel acid-sensitive micelles improved its antitumor activity. Bioconjugate Chem. 23, 966–980 (2012).10.1021/bc2005945 ↗
97. Jin, Y. et al. Oxime linkage: a robust tool for the design of pH-sensitive polymeric drug carriers. Biomacromolecules 12, 3460–3468 (2011).10.1021/bm200956u ↗
98. Du, Y., Chen, W., Zheng, M., Meng, F. & Zhong, Z. pH-sensitive degradable chimaeric polymersomes for the intracellular release of doxorubicin hydrochloride. Biomaterials 33, 7291–7299 (2012).10.1016/j.biomaterials.2012.06.034 ↗
99. Ahmed, M. & Narain, R. Intracellular delivery of DNA and enzyme in active form using degradable carbohydrate-based nanogels. Mol. Pharm. 9, 3160–3170 (2012).10.1021/mp300255p ↗
100. Ren, D., Kratz, F. & Wang, S-W. Protein nanocapsules containing doxorubicin as a pH-responsive delivery system. Small 7, 1051–1060 (2011).10.1002/smll.201002242 ↗