Ph-responsive polymer–drug conjugates: design and progress
Abstract
Polymer-drug conjugates are becoming established as a shining platform for drug delivery. Incorporation of pH-responsive linker between drug and polymer is expected to realize triggered release of bioactive agents from conjugates in specific sites, either in mildly acidic extracellular matrices of tumor tissues or, after cellular internalization, in acidic endosomes and lysosomes. As an emerging drug delivery system, such pH-responsive polymer-drug conjugates are able to selectively deliver and activate drug molecules while reducing their systemic side-effects. In this review, we present the recent advances in pH-responsive polymer-drug conjugates with different chemical structures and architectures, and attempt to clarify their mechanism of action, synthesis and characterization technology. Furthermore, several promising approaches for the future will also be suggested.
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The ionic interaction can dissolve in response to pH changes, causing the drug to be released from the polymer backbone.
“The ionic interaction can dissolve in response to pH changes, causing the drug to be released from the polymer backbone (Pang et al., 2016; Deirram et al., 2019).”
From pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery. (2023) · cites this paper as Pang et al., 2016
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Sedláček, O., Studenovský, M., Větvička, D., Ulbrich, K., & Hrubý, M. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.07.038 · Cited by 19 · see citing works
Wang, Y., Zhang, X., Xu, Z., et al. (2014) · Journal of Materials Science · doi:10.1007/s10853-014-8461-3 · Cited by 10 · see citing works
Tritylated oncolytics as prodrugs
Patel, V. F., Hardin, J. N., Grindey, G. B., et al. (1995) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/0960-894x(95)00063-y · Cited by 8 · see citing works
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pH-responsive polymer nanoparticles for drug delivery
Deirram, N., Zhang, C., Kermaniyan, S. S., Johnston, A. P. R., & Such, G. K. (2019) · Macromolecular Rapid Communications · doi:10.1002/marc.201800917 · Cited by 531 · see citing works
Poly(2-oxazoline)s based biomaterials: a comprehensive and critical update
Lorson, T., Lübtow, M. M., Wegener, E., Haider, M. S., Borova, S., Nahm, D., Jordan, R., Sokolski-Papkov, M., Kabanov, A. V., & Luxenhofer, R. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.05.022 · Cited by 391 · see citing works
<scp>pH</scp> ‐responsive polymers for drug delivery: Trends and opportunities
Singh, J., & Nayak, P. (2023) · Journal of Polymer Science · doi:10.1002/pol.20230403 · Cited by 327 · see citing works
<scp>pH</scp> ‐sensitive polymers: Classification and some fine potential applications
Ofridam, F., Tarhini, M., Lebaz, N., Gagnière, É., Mangin, D., & Elaissari, A. (2021) · Polymers for Advanced Technologies · doi:10.1002/pat.5230 · Cited by 286 · see citing works
pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery.
Vegad, U., Patel, M., Khunt, D., Zupančič, O., Chauhan, S., & Paudel, A. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1270364 · Cited by 85 · see citing works
“The ionic interaction can dissolve in response to pH changes, causing the drug to be released from the polymer backbone (Pang et al., 2016; Deirram et al., 2019).”
BackgroundpH-Responsive Natural Polymers as Versatile Carriers for Drug Delivery in Breast Cancer: A Review
Velapure, P. D., Chakote, S. R., Kansal, D., Barooah, A., Pawde, D. M., & Bobade, C. D. (2026) · Biomedical Materials & Devices · doi:10.1007/s44174-025-00427-w · Cited by 5 · see citing works
- Authors
- Pang, X., Jiang, Y., Xiao, Q., Leung, A. W., Hua, H., & Xu, C.
- Affiliations
- Chinese University of Hong Kong (HK)
- Corresponding author
- Xu, Chuanshan
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 222
- Pages
- 116-129
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2200680635
- Cited by
- 317
- References
- 114
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 32 · 2023: 33 · 2022: 29 · 2021: 34 · 2020: 33 · 2019: 45 · 2018: 34 · 2017: 32 · 2016: 13
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hong Kong research grant committee (476912)
- Health and Medical Research Fund (1100502)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- pH-responsive polymers, polymer-drug conjugates, triggered drug release, targeted drug delivery, conjugate synthesis
- MeSH terms
- Pharmaceutical Preparations, Hydrogen-Ion Concentration, Polymers, Drug Design, Drug Delivery Systems
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