Design of Environment‐Sensitive Supramolecular Assemblies for Intracellular Drug Delivery: Polymeric Micelles that are Responsive to Intracellular pH Change
Abstract
Drug smuggling: Micelles made up of block copolymers and the anticancer drug adriamycin (ADR), which is linked to the polymer by a pH-sensitive linker, have been prepared (see picture). Treatment of cancer cells with the micelles shows that the micelles are transported into the cell by endocytosis, thus bypassing the cell-membrane transporters. In the cell, the decrease in pH value triggers the release of the ADR, which retains its cytotoxic effect. The released ADR fluoresces which allows its localization within the cells to be detected.
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Tumor microenvironment has a mildly acidic pH (~6.8).
“For example, a pH-sensitive micellar system may be used in drug delivery to tumors, as reports confirm a mildly acidic pH (~6.8) in the tumor microenvironment.35”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [35]
Cites
Multicomponent Reactions with Isocyanides
Dömling, A. S. S., & Ugi, I. (2000) · Angewandte Chemie International Edition · doi:10.1002/1521-3773(20000915)39:18 · Cited by 4,079 · see citing works
Block copolymer micelles for drug delivery: design, characterization and biological significance
Kataoka, K., Harada, A., & Nagasaki, Y. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00124-1 · Cited by 3,506 · see citing works
Self-citationToward Self-Organization and Complex Matter
Lehn, J. (2002) · ChemInform · doi:10.1002/chin.200240281 · Cited by 2,279 · see citing works
Discher, D., & Eisenberg, A. (2002) · Science · doi:10.1126/science.1074972 · Cited by 2,251 · see citing works
Block copolymer micelles as vehicles for drug delivery
Kataoka, K., Kwon Glenn, S., Masayuki, Y., Teruo, O., & Sakurai, Y. (1993) · Journal of Controlled Release · doi:10.1016/0168-3659(93)90172-2 · Cited by 878 · see citing works
Self-citationLanger, R. (2001) · Science · doi:10.1126/science.1063273 · Cited by 580 · see citing works
Development of the polymer micelle carrier system for doxorubicin
Nakanishi, T., Fukushima, S., Okamoto, K., Suzuki, M., Matsumura, Y., Yokoyama, M., Okano, T., Sakurai, Y., & Kataoka, K. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00341-8 · Cited by 570 · see citing works
Self-citationHarada, A., & Kataoka, K. (1998) · Macromolecules · doi:10.1021/ma971277v · Cited by 482 · see citing works
Self-citationKatayose, S., & Kataoka, K. (1997) · Bioconjugate Chemistry · doi:10.1021/bc9701306 · Cited by 471 · see citing works
Self-citationDuncan, R. (1992) · Anti-Cancer Drugs · doi:10.1097/00001813-199206000-00001 · Cited by 445 · see citing works
Kwon, G., Suwa, S., Yokoyama, M., Okano, T., Sakurai, Y., & Kataoka, K. (1994) · Journal of Controlled Release · doi:10.1016/0168-3659(94)90118-x · Cited by 409 · see citing works
Self-citationKakizawa, Y., Harada, A., & Kataoka, K. (1999) · Journal of the American Chemical Society · doi:10.1021/ja993057y · Cited by 331 · see citing works
Self-citationPolyester Dendritic Systems for Drug Delivery Applications: Design, Synthesis, and Characterization
Ihre, H. R., Jesús, O. L. P. D., Szoka, F. C., & Fréchet, J. M. J. (2002) · Bioconjugate Chemistry · doi:10.1021/bc010102u · Cited by 329 · see citing works
Masayuki, Y., Miyauchi, M., Yamada, N., Teruo, O., Sakurai, Y., Kataoka, K., & Inoue, S. (1990) · Journal of Controlled Release · doi:10.1016/0168-3659(90)90139-k · Cited by 290 · see citing works
Self-citationNagasaki, Y., OKADA, T., Scholz, C., Iijima, M., Kato, M., & Kataoka, K. (1998) · Macromolecules · doi:10.1021/ma971294k · Cited by 245 · see citing works
Self-citationSelective Delivery of Adiramycin to a Solid Tumor Using a Polymeric Micelle Carrier System
Yokoyama, M., Okano, T., Sakurai, Y., Fukushima, S., Okamoto, K., & Kataoka, K. (1999) · Journal of drug targeting · doi:10.3109/10611869909085500 · Cited by 213 · see citing works
Self-citationKaneko, T., Willner, D., Monković, I., Knipe, J. O., Braslawsky, G. R., Greenfield, R. S., & Vyas, D. M. (1991) · Bioconjugate Chemistry · doi:10.1021/bc00009a001 · Cited by 163 · see citing works
Giant Amphiphiles by Cofactor Reconstitution
Boerakker, M. J., Hannink, J. M., Bomans, P. H. H., Frederik, P. M., Nolte, R. J. M., Meijer, E. M., & Sommerdijk, N. A. J. M. (2002) · Angewandte Chemie International Edition · doi:10.1002/1521-3773(20021115)41:22 · Cited by 146 · see citing works
Control of Architecture in Block-Copolymer Vesicles
Shen, H., & Eisenberg, A. (2000) · Angewandte Chemie · doi:10.1002/1521-3757(20000915)112:18 · Cited by 138 · see citing works
Tang, A., Kopečková, P., & Kopec̆ek, J. (2003) · Pharmaceutical Research · doi:10.1023/a:1022639701388 · Cited by 45 · see citing works
pH-spaltbare molekulare Nanotransporter auf der Basis dendritischer Kern-Schale-Architekturen
Krämer, M., Stumbé, J., Türk, H., et al. (2002) · Angewandte Chemie · doi:10.1002/1521-3757(20021115)114:22 · Cited by 32 · see citing works
pH-Controlled Inclusion and Release of Oxyanions by Dendrimers Bearing Methyl Orange Moieties
Stephan, H., Spies, H., Johannsen, B., et al. (2000) · Organic Letters · doi:10.1021/ol006100r · Cited by 30 · see citing works
The NASA-NCI Collaboration on Biomolecular Sensors
Goldin, D. S., Dahl, C. A., Olsen, K. L., et al. (2001) · Science · doi:10.1126/science.1059744 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Engineered Nanoparticles for Drug Delivery in Cancer Therapy
Sun, T., Zhang, Y. S., Pang, B., Hyun, D. C., Yang, M., & Xia, Y. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201403036 · Cited by 2,164 · see citing works
Polymers for Drug Delivery Systems
Liechty, W. B., Kryscio, D. R., Slaughter, B. V., & Peppas, N. A. (2010) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-073009-100847 · Cited by 1,608 · see citing works
Block copolymer micelles in nanomedicine applications
Cabral, H., Miyata, K., Osada, K., & Kataoka, K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00199 · Cited by 1,309 · see citing works
Self-citationBiodegradable synthetic polymers: Preparation, functionalization and biomedical application
Tian, H., Tang, Z., Zhuang, X., Chen, X., & Jing, X. (2012) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2011.06.004 · Cited by 1,293 · see citing works
Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery
Rapoport, N. (2007) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2007.05.009 · Cited by 1,002 · see citing works
Progress of drug-loaded polymeric micelles into clinical studies
Cabral, H., & Kataoka, K. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.06.042 · Cited by 837 · see citing works
Self-citationWang, F., Wang, Y.-C., Dou, S., Xiong, M.-H., Sun, T.-M., & Wang, J. (2011) · ACS Nano · doi:10.1021/nn200007z · Cited by 813 · see citing works
Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles
Singh, A. P., Biswas, A., Shukla, A., & Maiti, P. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0068-3 · Cited by 645 · see citing works
Atrp in the design of functional materials for biomedical applications
Siegwart, D. J., Oh, J. K., & Matyjaszewski, K. (2012) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2011.08.001 · Cited by 613 · see citing works
Multi-Stimuli Sensitive Amphiphilic Block Copolymer Assemblies
Klaikherd, A., Nagamani, C., & Thayumanavan, S. (2009) · Journal of the American Chemical Society · doi:10.1021/ja809475a · Cited by 594 · see citing works
Functionalized micellar systems for cancer targeted drug delivery
Sutton, D., Nasongkla, N., Blanco, E., & Gao, J. (2007) · Pharmaceutical Research · doi:10.1007/s11095-006-9223-y · Cited by 557 · see citing works
Stimuli-responsive nanomaterials for therapeutic protein delivery
Lu, Y., Sun, W., & Gu, Z. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.08.015 · Cited by 415 · see citing works
pH- and ion-sensitive polymers for drug delivery
Yoshida, T., Lai, T. C., Kwon, G. S., & Sako, K. (2013) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2013.821978 · Cited by 367 · see citing works
Thermosensitive and biodegradable polymeric micelles for paclitaxel delivery
Soga, O., van Nostrum, C. F., Fens, M., Rijcken, C. J. F., Schiffelers, R. M., Storm, G., & Hennink, W. E. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.12.009 · Cited by 319 · see citing works
Yang, Z., Zhang, Y., Yang, Y., Sun, L., Han, D., Li, H., & Wang, C. (2010) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2009.11.007 · Cited by 311 · see citing works
Polymeric micelles: authoritative aspects for drug delivery
Kulthe, S. S., Choudhari, Y. M., Inamdar, N. N., & Mourya, V. (2012) · Designed Monomers and Polymers · doi:10.1080/1385772x.2012.688328 · Cited by 235 · see citing works
Osada, K., Christie, R. J., & Kataoka, K. (2009) · Journal of The Royal Society Interface · doi:10.1098/rsif.2008.0547.focus · Cited by 218 · see citing works
Self-citationFuture of the Particle Replication in Nonwetting Templates (PRINT) Technology
Xu, J., Wong, D. H. C., Byrne, J. D., Chen, K., Bowerman, C., & DeSimone, J. M. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201209145 · Cited by 208 · see citing works
Tang, R., Ji, W., Panus, D., Palumbo, R. N., & Wang, C. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.12.005 · Cited by 202 · see citing works
Shi, C., Guo, X., Qu, Q., Tang, Z., Wang, Y., & Zhou, S. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.06.036 · Cited by 189 · see citing works
Poly(PS-b-DMA) micelles for reactive oxygen species triggered drug release
Gupta, M. K., Meyer, T. A., Nelson, C. E., & Duvall, C. L. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.07.042 · Cited by 171 · see citing works
Liu, R., Li, D., He, B., Xu, X., Sheng, M., Lai, Y., Wang, G., & Gu, Z. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.02.031 · Cited by 157 · see citing works
Recent Advances in Nanomicelles Delivery Systems.
Tawfik, S. M., Azizov, S., Elmasry, M. R., Sharipov, M., & Lee, Y.-I. (2020) · Nanomaterials · doi:10.3390/nano11010070 · Cited by 156 · see citing works
“A novel class of self-assembling amphiphilic blocks, poly(ethylene glycol)-poly(aspartate hydrazone adriamycin) (PEG-P(Asp-Hyd-ADR), was specifically developed and prepared by conjugating adriamycin (ADR) to the side chain of the core-forming PAsp competent via the pH-sensitive hydrazone bond [144].”
MethodThambi, T., Yoon, H. Y., Kim, K., Kwon, I. C., Yoo, C. K., & Park, J. H. (2011) · Bioconjugate Chemistry · doi:10.1021/bc2000963 · Cited by 138 · see citing works
Fu, L., Sun, C., & Yan, L. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/am508291k · Cited by 78 · see citing works
Assessing the benefits of drug delivery by nanocarriers: a partico/pharmacokinetic framework
Siegel, R. A., Kirtane, A. R., & Panyam, J. (2017) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2016.2632733 · Cited by 14 · see citing works
- Authors
- Bae, Y., Fukushima, S., Harada, A., & Kataoka, K.
- Affiliations
- The University of Tokyo (JP)
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2003-10
- Volume
- 42
- Issue
- 38
- Pages
- 4640-4643
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2120915183
- Cited by
- 1,329
- References
- 23
- Citations by year
- 2026: 20 · 2025: 18 · 2024: 15 · 2023: 18 · 2022: 35 · 2021: 34 · 2020: 68 · 2019: 55 · 2018: 60 · 2017: 63 · 2016: 112 · 2015: 95 · 2014: 117 · 2013: 107 · 2012: 106
- FWCI
- 12.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- polymeric micelles, pH-responsive drug delivery, intracellular drug delivery, doxorubicin, block copolymers, pH-sensitive linker, endocytosis, intracellular pH, anticancer drug release, supramolecular self-assembly
- MeSH terms
- Cell Division, Doxorubicin, Humans, Hydrogen-Ion Concentration, Micelles, Polymers, Time Factors, Drug Delivery Systems, Carcinoma, Small Cell, Cell Line, Tumor
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