A siramesine-loaded metal organic framework nanoplatform for overcoming multidrug resistance with efficient cancer cell targeting

• Published in: RSC advances Vol. 1; no. 12; pp. 6919 - 6926
• Main Authors: Liu, Jiahui, Tang, Menghuan, Zhou, Yanghao, Long, Yijuan, Cheng, Yuan, Zheng, Huzhi
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 14-02-2020; The Royal Society of Chemistry
• Subjects: Anticancer properties; Apoptosis; Biocompatibility; Biomedical materials; Cancer therapies; Central nervous system; Chemistry; Chemotherapy; Drug delivery systems; Life expectancy; Metal-organic frameworks; Toxicity; Zeta potential
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c9ra09923a

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.
ZIF-8@Sira/FA induces the cancer cells apoptosis and then eliminates cancer cells from the inside through the lysosomal death pathway.