pH-sensitive pluronic micelles combined with oxidative stress amplification for enhancing multidrug resistance breast cancer therapy
Abstract
Multidrug resistance (MDR) is one of the major obstacles to clinical cancer chemotherapy. Herein, we designed new pH-sensitive pluronic micelles with the synergistic effects of oxidative therapy and MDR reversal. Pluronic (P123) was modified with α-tocopheryl succinate (α-TOS) via an acid-labile ortho ester (OE) linkage to give a pH-sensitive copolymer (POT). Self-assembled POT micelles exhibited desirable size (~80 nm), excellent anti-dilution ability, high drug loading (~85%), acid-triggered degradation and drug release behaviours. In vitro cell experiments verified that POT micelles could significantly reverse MDR through suppressing the function of drug effluxs mediated by P123 and induce more reactive oxygen species (ROS) generation mediated by α-TOS, resulting in enhanced cytotoxicity and apoptosis in MDR cells. In vivo studies further revealed that DOX-loaded POT micelles (POT-DOX) possessed the highest drug accumulation (3.03% ID/g at 24 h) and the strongest tumour growth inhibition (TGI 83.48%). Pathological analysis also indicated that POT-DOX could induce more apoptosis or necrosis at the site of tumour without distinct damage to normal tissues. Overall, these smart POT micelles have great potential as promising nano-carriers for MDR reversal and cancer treatment.
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The occurrence of multidrug resistance of cancer cells reduces the efficacy of chemotherapeutic drugs and has become the most crucial reason for the failure of hepatocellular carcinoma treatment.
“Especially, the occurrence of multidrug resistance (MDR) of cancer cells can reduce the efficacy of chemotherapeutic drugs,6,7 which has become the most crucial reason for the failure of HCC treatment.”
Multidrug resistance contributes to reduced sensitivity of cancer cells to chemotherapeutic drugs, mainly owing to over-expression of drug efflux transporters.
“Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters.”
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Liang, X., Wang, Y., Shi, H., Dong, M., Han, H., & Li, Q. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s304526 · Cited by 41 · see citing works
- Authors
- Cheng, X., Zeng, X., Zheng, Y., Fang, Q., Wang, X., Wang, J., & Tang, R.
- Affiliations
- Anhui University (CN)
- Corresponding author
- Tang, Rupei
- Venue
- Journal of Colloid and Interface Science
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 565
- Pages
- 254-269
- ISSN
- 0021-9797 (ISSN-L)
- OpenAlex
- W2998931050
- Cited by
- 41
- References
- 63
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 14 · 2020: 5
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Colloid and Interface Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (51803001, 51603001, 51503001)
- Research Foundation of Education Department of Anhui Province of China (KJ2018ZD003, KJ2018A0006)
- Anhui University (AU02303203)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- Pluronic P123, pH-responsive micelles, multidrug resistance reversal, oxidative stress, alpha-tocopheryl succinate, reactive oxygen species, drug efflux inhibition, doxorubicin delivery, breast cancer, nanocarriers, apoptosis, tumor growth inhibition
- MeSH terms
- Animals, Antineoplastic Agents, Breast Neoplasms, Doxorubicin, Drug Screening Assays, Antitumor, Female, Humans, Hydrogen-Ion Concentration, Mammary Neoplasms, Experimental, Micelles, Particle Size, Poloxalene, Surface Properties, Tumor Cells, Cultured, Molecular Structure, Apoptosis, Oxidative Stress, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Cell Proliferation, Mice, MCF-7 Cells
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