One-Step Self-Assembling Nanomicelles for Pirarubicin Delivery To Overcome Multidrug Resistance in Breast Cancer
Abstract
Tumor cells can acquire multidrug resistance (MDR) as a result of drug efflux mediated by P-glycoprotein (P-gp). Here we report a targeted delivery system to carry pirarubicin (THP) to MDR breast cancer both in vitro and in vivo . PEG-derivatized vitamin E (PAMV 6 ) amphiphiles loaded with THP were self-assembled in a single step. The PAMV 6 micelles showed unimodal size distribution and high drug loading efficiency. Cytotoxicity of PAMV 6 /THP was higher than that of free THP on MCF-7/ADR cells but comparable to that of THP on MCF-7 cells. PAMV 6 /THP was able to reverse MDR more than free THP in MCF-7/ADR cells, likely reflecting the remarkably higher intracellular THP concentration in micelle-treated cells and PAMV 6 -mediated inhibition of P-gp activity. PAMV 6 /THP micelles were internalized into MCF-7/ADR cells via macropinocytosis and caveolin-mediated endocytosis, further avoiding P-gp-mediated efflux. Mechanistic studies revealed that blank PAMV 6 micelles inhibited P-gp activity but did not affect P-gp expression, by significantly reducing mitochondrial membrane potential and slightly decreasing intracellular ATP levels. In a nude mouse xenograft model, PAMV 6 /THP led to much greater THP accumulation in tumors and much slower tumor growth than free THP. At the same time, PAMV 6 /THP was associated with significantly less severe bone marrow suppression and organ toxicity than free THP. Our results indicate that this PAMV 6 -based micelle system holds promise for combating MDR in cancer therapy.
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Polymeric nanomicelles (PNMs) employ passive targeting, folate, pH-sensitive, and thermosensitive DDSs to beat drug resistance through perfect targeting.
“PNMs employ passive targeting, folate, pH-sensitive, and thermosensitive DDSs to beat drug resistance through perfect targeting (Figure 4) [101,102,103,104].”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [103]
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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
- Authors
- Li, Y., Li, R., Liu, Q., Li, W., Zhang, T., Zou, M., Li, H., Wu, T., Cheng, S., Su, Z., Zhang, Z., & He, J.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- He, Jinhan
- ORCID
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-10-21
- Volume
- 13
- Issue
- 11
- Pages
- 3934-3944
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W2531792064
- Cited by
- 16
- References
- 38
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 2
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81471068, 81603035)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- pirarubicin, multidrug resistance, breast cancer, P-glycoprotein, amphiphilic molecules, targeted drug delivery, macropinocytosis, caveolin-mediated endocytosis, mitochondrial membrane potential, MCF-7/ADR cells, tumor xenografts, drug efflux inhibition
- MeSH terms
- Adenosine Triphosphate, Animals, Cell Adhesion, Cell Cycle, Doxorubicin, Humans, Mice, Nude, Micelles, Rats, Wistar, Cell Line, Tumor, Mice, Rats, Membrane Potential, Mitochondrial, MCF-7 Cells
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