Pluronics and MDR reversal: an update
Open accessAbstract
Multidrug resistance (MDR) remains one of the biggest obstacles for effective cancer therapy. Currently there are only few methods that are available clinically that are used to bypass MDR with very limited success. In this review we describe how MDR can be overcome by a simple yet effective approach of using amphiphilic block copolymers. Triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), arranged in a triblock structure PEO-PPO-PEO, Pluronics or “poloxamers”, raised a considerable interest in the drug delivery field. Previous studies demonstrated that Pluronics sensitize MDR cancer cells resulting in increased cytotoxic activity of Dox, paclitaxel, and other drugs by 2–3 orders of magnitude. Pluronics can also prevent the development of MDR in vitro and in vivo. Additionally, promising results of clinical studies of Dox/Pluronic formulation reinforced the need to ascertain a thorough understanding of Pluronic effects in tumors. These effects are extremely comprehensive and appear on the level of plasma membranes, mitochondria, and regulation of gene expression selectively in MDR cancer cells. Moreover, it has been demonstrated recently that Pluronics can effectively deplete tumorigenic intrinsically drug-resistant cancer stem cells (CSC). Interestingly, sensitization of MDR and inhibition of drug efflux transporters is not specific or selective to Pluronics. Other amphiphilic polymers have shown similar activities in various experimental models. This review summarizes recent advances of understanding the Pluronic effects in sensitization and prevention of MDR.
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Certain Pluronic block copolymers can act as biological response modifiers that sensitize multidrug-resistant and cancer stem cells to anticancer chemotherapeutics.
“A notable property of select Pluronic® block copolymers to act as biological response modifiers to sensitize multidrug resistant (MDR) and cancer stem cells with respect to anticancer chemotherapeutics was widely reported and reviewed from mechanistic and translational points of view [25, 104].”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [104]
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Hwang, D., Ramsey, J. D., & Kabanov, A. V. (2020) · Advanced drug delivery reviews · doi:10.1016/j.addr.2020.09.009 · Cited by 699 · see citing works
“A notable property of select Pluronic block copolymers to act as biological response modifiers to sensitize multidrug resistant (MDR) and cancer stem cells with respect to anticancer chemotherapeutics waswidely reported and reviewed frommechanistic and translational points of view [25,104].”
BackgroundSelf-citation50 years of oral lipid-based formulations: provenance, progress and future perspectives
Feeney, O. M., Crum, M. F., McEvoy, C. L., Trevaskis, N. L., Williams, H. D., Pouton, C. W., Charman, W. N., Bergström, C. A. S., & Porter, C. J. H. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.04.007 · Cited by 426 · see citing works
- Authors
- Alakhova, D. Y., & Kabanov, A. V.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Kabanov, Alexander V.
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-06-20
- Volume
- 11
- Issue
- 8
- Pages
- 2566-2578
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- PMC
- PMC4122590
- OpenAlex
- W2007080192
- Cited by
- 224
- References
- 136
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 12 · 2023: 18 · 2022: 14 · 2021: 18 · 2020: 23 · 2019: 21 · 2018: 26 · 2017: 25 · 2016: 28 · 2015: 17 · 2014: 1
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Pharmaceutics (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Cancer Institute (2R01 CA89225, U01CA151806, R01CA089225, UO1 CA151806)
- National Institute of General Medical Sciences (P20GM103480)
- National Center for Research Resources (P20RR021937)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- poloxamer, multidrug resistance, multidrug resistance reversal, amphiphilic block copolymers, PEO-PPO-PEO triblock copolymer, doxorubicin, paclitaxel, efflux pumps, cancer stem cells, drug delivery, tumor cell membrane, mitochondria, gene expression regulation
- MeSH terms
- Animals, Biological Transport, Cell Membrane, Humans, Lipids, Mitochondria, Neoplasms, Polyethylene Glycols, Propylene Glycols, Neoplastic Stem Cells, Drug Delivery Systems, Apoptosis, Drug Resistance, Multiple, Drug Resistance, Neoplasm, ATP Binding Cassette Transporter, Subfamily B, Member 1, Poloxamer, Membrane Microdomains, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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