AI Article Synopsis
- - Drug resistance poses a significant challenge in cancer treatment, but targeting mitochondria with specialized drugs shows promise for overcoming this issue by effectively targeting resistant cancer cells.
- - The researchers developed a new compound called polymerized dequalinium, which showed lower toxicity and better gene delivery capabilities compared to the standard dequalinium.
- - The study also introduced a fusion aptamer designed to deliver the chemotherapy drug doxorubicin specifically to tumor cells, enhancing drug release and effectiveness against drug-resistant cancer cells while improving mitochondrial targeting and stability.
Article Abstract
Drug resistance is one of the major obstacles to the success of cancer chemotherapy. Mitochondrial targeting drugs are increasingly thought to be able to eradicate resistant cancer cells. However, immature drug release outside mitochondria and the absence of multifunctional targeting carriers against tumor mitochondria greatly limit the corresponding therapeutic benefits. Here, we synthesized polymerized dequalinium by integrating dequalinium, lysine, and poly(ethylene glycol) for mitochondrial targeting. The polymerized dequalinium exhibited lower cytotoxicity and stronger gene condensing ability than free dequalinium. We designed AS1411-ATP fusion aptamer to load doxorubicin (DOX) for both tumor targeting and ATP-responsive DOX release. The polyplexes by polymerized dequalinium and bifunctional aptamer can target tumor cells AS1411 and show improved stability, mitochondrial targeting, DOX release in response to mitochondrial ATP, and enhanced apoptosis-inducing effect on DOX-resistant MCF-7/DOX cells. The present study highlights a promising application of the polyplexes in reversing drug resistance in tumor cells tumor mitochondrial targeting drug release.
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| http://dx.doi.org/10.1021/acsabm.0c00610 | DOI Listing |
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