Trackable Mitochondria-Targeting Nanomicellar Loaded with Doxorubicin for Overcoming Drug Resistance
Abstract
Multidrug resistance (MDR) has been recognized as a major obstacle to successful chemotherapy for cancer in the clinic. In recent years, more and more nanoscaled drug delivery systems (DDS) are constructed to modulate drug efflux protein (P-gp) and deliver chemotherapeutic drugs for overcoming MDR. Among them, d -α-tocopheryl polyethylene glycol succinate (TPGS) has been widely used as a drug carrier due to its capability of inhibiting overexpression of P-gp and good amphiphilicity favorable for improving permeation and long-circulation property of DDS. In the present work, a novel kind of mitochondria-targeting nanomicelles-based DDS is developed to integrate chemotherapeutics delivery with fluorescence imaging functionalities on a comprehensive nanoplatform. The mitochondria-targeting nanomicelles are prepared by self-assembly of triphenylphosphine (TPP)-modified TPGS and fluorescent carbon quantum dots (CQDs) in an n -hexane/H 2 O mixed solution, named CQDs-TPGS-TPP. Notably, although the drug loading content of doxorubicin (DOX) in the as-prepared nanomicelles is as low as 3.4%, the calculated resistant index (RI) is greatly decreased from 66.23 of free DOX to 7.16 of DOX-loaded nanomicelles while treating both parental MCF-7 cells and drug-resistant MCF-7/ADR cells. Compared with free DOX, the penetration efficiency of DOX-loaded nanomicelles in three-dimensional multicellular spheroids (MCs) of MCF-7/ADR is obviously increased. Moreover, the released DOX from the nanomicelles can cause much more damage to cells of drug-resistant MCs. These results demonstrate that our constructed mitochondria-targeting nanomicelles-based DDS have potential application in overcoming MDR of cancer cells as well as their MCs that mimic in vivo tumor tissues. The MDR-reversal mechanism of the DOX-loaded CQDs-TPGS-TPP nanomicelles is also discussed.
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Nanomicelles have shown lower dissociation kinetics after dilution, around 1000-fold slower compared to conventional surfactant micelles.
“As reported, the nanomicelles have shown lower dissociation kinetics after dilution around 1000-fold slower compared to conventional surfactant micelles.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [11]
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- Authors
- Zhang, Y., Zhang, C., Chen, J., Liu, L., Hu, M., Li, J., & Bi, H.
- Affiliations
- Anhui University (CN)
- Anhui Medical University (CN)
- Corresponding author
- Bi, Hong
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-07-24
- Volume
- 9
- Issue
- 30
- Pages
- 25152-25163
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2734768350
- Cited by
- 109
- References
- 67
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 13 · 2023: 14 · 2022: 10 · 2021: 21 · 2020: 13 · 2019: 12 · 2018: 14 · 2017: 2
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Anhui University
- National Natural Science Foundation of China (51272002)
- Foundation for Imported Leading Talent Teams in Universities and Colleges of Anhui Province
- 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
- doxorubicin, multidrug resistance, P-glycoprotein inhibition, TPGS, triphenylphosphine, carbon quantum dots, fluorescence imaging, drug delivery systems, MCF-7/ADR cells, tumor spheroids, drug penetration, drug resistance reversal
- MeSH terms
- Doxorubicin, Drug Carriers, Humans, Micelles, Mitochondria, Polyethylene Glycols, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Cell Line, Tumor, Nanostructures
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