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A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
Multi-targeted inhibition of tumor growth and lung metastasis by redox-sensitive shell crosslinked micelles loading
Xiaopin Duan1, Jisheng Xiao, Qi Yin
1Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Abstract:
Metastasis, the main cause of cancer related deaths, remains the greatest challenge in cancer treatment. Disulfiram (DSF), which has multi-targeted anti-tumor activity, was encapsulated into redox-sensitive shell crosslinked micelles to achieve intracellular targeted delivery and finally inhibit tumor growth and metastasis. The crosslinked micelles demonstrated good stability in circulation and specifically released DSF under a reductive environment that mimicked the intracellular conditions of tumor cells. As a result, the DSF-loaded redox-sensitive shell crosslinked micelles (DCMs) dramatically inhibited cell proliferation, induced cell apoptosis and suppressed cell invasion, as well as impairing tube formation of HMEC-1 cells. In addition, the DCMs could accumulate in tumor tissue and stay there for a long time, thereby causing significant inhibition of 4T1 tumor growth and marked prevention in lung metastasis of 4T1 tumors. These results suggested that DCMs could be a promising delivery system in inhibiting the growth and metastasis of breast cancer.
Insights
This study developed novel Disulfiram-loaded redox-sensitive micelles (DCMs) to target cancer cells. DCMs effectively inhibited tumor growth and metastasis, offering a promising approach for breast cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Metastasis is a primary cause of cancer mortality and a significant challenge in cancer therapy.
- Disulfiram (DSF) exhibits multi-targeted anti-tumor properties.
- Developing effective drug delivery systems is crucial for improving cancer treatment outcomes.
Purpose of the Study:
- To create redox-sensitive shell crosslinked micelles for targeted intracellular delivery of Disulfiram (DSF).
- To evaluate the efficacy of DSF-loaded micelles (DCMs) in inhibiting tumor growth and metastasis.
- To assess the potential of DCMs as a novel therapeutic strategy for breast cancer.
Main Methods:
- Encapsulation of Disulfiram (DSF) into redox-sensitive shell crosslinked micelles.
- Evaluation of micelle stability in circulation and drug release under reductive conditions.
- In vitro assessment of DCMs on cancer cell proliferation, apoptosis, invasion, and tube formation.
- In vivo studies to evaluate DCMs' tumor accumulation, growth inhibition, and metastasis prevention in a 4T1 breast cancer model.
Main Results:
- The developed crosslinked micelles showed good stability and specifically released DSF in a reductive environment mimicking tumor intracellular conditions.
- DCMs significantly inhibited cancer cell proliferation, induced apoptosis, suppressed invasion, and impaired tube formation in vitro.
- DCMs demonstrated enhanced accumulation in tumor tissues and prolonged retention.
- Significant inhibition of 4T1 tumor growth and marked prevention of lung metastasis were observed in vivo.
Conclusions:
- DSF-loaded redox-sensitive shell crosslinked micelles (DCMs) represent a promising drug delivery system for cancer therapy.
- DCMs effectively target tumor cells and inhibit tumor growth and metastasis.
- This nanotechnology-based approach holds potential for improving the treatment of breast cancer and other metastatic cancers.
