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Published on: June 13, 2014
A siramesine-loaded metal organic framework nanoplatform for overcoming multidrug resistance with efficient cancer
Jiahui Liu1, Menghuan Tang1, Yanghao Zhou2
1Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University Chongqing 400715 P. R. China zhenghz@swu.edu.cn.
Abstract:
Cancer is the leading cause of death and the most important obstacle to increasing life expectancy. With the sophisticated design and research of anticancer drugs, multidrug resistance to chemotherapy has become more and more common. After the emergence of multidrug resistance, the development of a new drug is beset with difficulties. The repurposing of non-anticancer drugs is thus a timely strategy for cancer therapy. Here, we highlight the potential of repurposing siramesine, a central nervous system drug for antitumor research and we construct a metal organic framework-based nanoplatform for effective intracellular accumulation and pH-response siramesine release. The released drug induces lysosome membrane permeabilization, leading to lysosomal cathepsins leakage and then results in cell apoptosis. Due to the modification of folic acids, the constructed drug delivery nanosystem shows good biocompatibility and efficient cancer cell targeting. Importantly, the drug delivery system shows enhanced anticancer efficacy in vitro, which not only effectively kills cancer cells but also kills multidrug resistant cells. Thus, the drug delivery nanosystem constructed in this study is thought to become a promising anticancer agent for cancer therapy and even overcoming multidrug resistance, which provides good prospects for biomedical applications.
Insights
Repurposing the central nervous system drug siramesine into a targeted nanoplatform effectively kills cancer cells, including multidrug-resistant types. This novel drug delivery system shows promise for overcoming chemotherapy resistance and advancing cancer therapy.
Area of Science:
- Oncology
- Nanomedicine
- Drug Discovery
Background:
- Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy, limiting treatment efficacy and patient survival.
- Developing novel anticancer agents is difficult, making drug repurposing a valuable strategy.
Purpose of the Study:
- To investigate the potential of repurposing siramesine, a central nervous system drug, for cancer therapy.
- To develop a metal-organic framework (MOF)-based nanoplatform for targeted delivery and pH-responsive release of siramesine.
Main Methods:
- Construction of a MOF-based nanoplatform encapsulating siramesine.
- Modification of the nanoplatform with folic acid for enhanced cancer cell targeting.
- Evaluation of intracellular drug accumulation, pH-responsive release, and anticancer efficacy in vitro.
- Assessment of the mechanism of action, including lysosomal membrane permeabilization and apoptosis induction.
Main Results:
- The developed nanoplatform demonstrated effective intracellular accumulation and triggered siramesine release in response to acidic pH.
- Folic acid modification ensured good biocompatibility and efficient targeting of cancer cells.
- The siramesine-loaded nanoplatform exhibited enhanced anticancer efficacy against both conventional and multidrug-resistant cancer cells in vitro.
- The drug delivery system induced cancer cell apoptosis via lysosomal membrane permeabilization and cathepsin leakage.
Conclusions:
- The MOF-based nanoplatform offers a promising approach for siramesine delivery in cancer therapy.
- This strategy effectively overcomes multidrug resistance, presenting significant potential for clinical applications.
- The targeted drug delivery system provides a novel avenue for developing advanced anticancer agents.
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