Related Experiment Video
Updated: Oct 6, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Polyplexes by Polymerized Dequalinium and Bifunctional Aptamer for Mitochondrial Targeting Drug Release to Overcome
Duo Gao1, Qiuning Zhu1, Jianqing Ruan1
1Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
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 via 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 via tumor mitochondrial targeting drug release.
Insights
This study developed novel mitochondrial-targeting nanoparticles to overcome cancer drug resistance. These nanoparticles deliver chemotherapy drugs specifically to tumor mitochondria, enhancing efficacy against resistant cancer cells.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Drug resistance is a major challenge in cancer chemotherapy.
- Mitochondrial targeting drugs show potential for eradicating resistant cancer cells.
- Limitations include premature drug release and lack of multifunctional carriers for tumor mitochondria.
Purpose of the Study:
- To synthesize a novel drug delivery system for targeting tumor mitochondria and overcoming drug resistance.
- To develop a system capable of controlled drug release within mitochondria.
- To enhance the efficacy of chemotherapy against drug-resistant cancer cells.
Main Methods:
- Synthesized polymerized dequalinium for mitochondrial targeting.
- Created an AS1411-ATP fusion aptamer to load doxorubicin (DOX) for tumor targeting and ATP-responsive release.
- Formulated polyplexes using polymerized dequalinium and the bifunctional aptamer.
Main Results:
- Polymerized dequalinium showed lower cytotoxicity and enhanced gene condensing ability compared to free dequalinium.
- The polyplexes effectively targeted tumor cells via AS1411.
- Achieved improved stability, mitochondrial targeting, and ATP-responsive DOX release.
- Demonstrated enhanced apoptosis induction in DOX-resistant MCF-7/DOX cells.
Conclusions:
- The developed polyplexes show promise for reversing tumor drug resistance.
- Mitochondrial targeting and controlled drug release are key to enhanced therapeutic benefits.
- This approach offers a potential strategy for treating drug-resistant cancers.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
01:39Mitochondrial Protein Sorting
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...