Doxorubicin-Tethered Responsive Gold Nanoparticles Facilitate Intracellular Drug Delivery for Overcoming Multidrug Resistance in Cancer Cells
Abstract
Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. Through the development of a drug delivery system that tethers doxorubicin onto the surface of gold nanoparticles with a poly(ethylene glycol) spacer via an acid-labile linkage (DOX-Hyd@AuNPs), we have demonstrated that multidrug resistance in cancer cells can be significantly overcome by a combination of highly efficient cellular entry and a responsive intracellular release of doxorubicin from the gold nanoparticles in acidic organelles. DOX-Hyd@AuNPs achieved enhanced drug accumulation and retention in multidrug resistant MCF-7/ADR cancer cells when it was compared with free doxorubicin. It released doxorubicin in response to the pH of acidic organelles following endocytosis, opposite to the noneffective drug release from doxorubicin-tethered gold nanoparticles via the carbamate linkage (DOX-Cbm@AuNPs), which was shown by the recovered fluorescence of doxorubicin from quenching due to the nanosurface energy transfer between the doxorubicinyl groups and the gold nanoparticles. DOX-Hyd@AuNPs therefore significantly enhanced the cytotoxicity of doxorubicin and induced elevated apoptosis of MCF-7/ADR cancer cells. With a combined therapeutic potential and ability to probe drug release, DOX-Hyd@AuNPs represent a model with dual roles in overcoming MDR in cancer cells and probing the intracellular release of drug from its delivery system.
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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.”
The multidrug resistance phenomenon is mainly attributed to over-expression of the ATP-binding cassette transporter family in cancer cells, including ABCG1, ABCC1 and ABCG2.
“The phenomenon was mainly attributed to the over-expression of ATP-binding cassette (ABC) transporter family in cancer cells, including ABCG1, ABCC1 and ABCG2.8–10”
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- Authors
- Wang, F., Wang, Y.-C., Dou, S., Xiong, M.-H., Sun, T.-M., & Wang, J.
- Affiliations
- University of Science and Technology of China (CN)
- Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
- Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, P. R. China
- Corresponding author
- Wang, Jun
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-04-12
- Volume
- 5
- Issue
- 5
- Pages
- 3679-3692
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2324209741
- Cited by
- 813
- References
- 54
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 31 · 2023: 43 · 2022: 64 · 2021: 56 · 2020: 67 · 2019: 67 · 2018: 67 · 2017: 67 · 2016: 74 · 2015: 68 · 2014: 68 · 2013: 59 · 2012: 33
- FWCI
- 21.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Electronic, Optical and Magnetic Materials › Gold and Silver Nanoparticles Synthesis and Applications
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- doxorubicin, gold nanoparticles, multidrug resistance, intracellular drug delivery, pH-responsive drug release, polyethylene glycol spacer, MCF-7/ADR cells, endocytosis, fluorescence quenching, surface energy transfer, apoptosis, cancer chemotherapy
- MeSH terms
- Antibiotics, Antineoplastic, Doxorubicin, Gold, Humans, Neoplasms, Experimental, Apoptosis, Drug Resistance, Multiple, Cell Line, Tumor, Nanocapsules
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