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A cell-targeted, size-photocontrollable, nuclear-uptake nanodrug delivery system for drug-resistant cancer therapy
Liping Qiu1, Tao Chen, Ismail Öçsoy
1Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University , Changsha 410082, China.
Abstract:
The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell-membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs from the cell, is a major mechanism of MDR. Nuclear-uptake nanodrug delivery systems, which enable intranuclear release of anticancer drugs, are expected to address this challenge by bypassing P-gp. However, before entering the nucleus, the nanocarrier must pass through the cell membrane, necessitating coordination between intracellular and intranuclear delivery. To accommodate this requirement, we have used DNA self-assembly to develop a nuclear-uptake nanodrug system carried by a cell-targeted near-infrared (NIR)-responsive nanotruck for drug-resistant cancer therapy. Via DNA hybridization, small drug-loaded gold nanoparticles (termed nanodrugs) can self-assemble onto the side face of a silver-gold nanorod (NR, termed nanotruck) whose end faces were modified with a cell type-specific internalizing aptamer. By using this size-photocontrollable nanodrug delivery system, anticancer drugs can be efficiently accumulated in the nuclei to effectively kill the cancer cells.
Insights
This study introduces a novel nanodrug delivery system using DNA self-assembly to overcome multidrug resistance (MDR) in cancer therapy. The system effectively delivers anticancer drugs into cancer cell nuclei, bypassing P-glycoprotein efflux mechanisms.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Multidrug resistance (MDR) is a significant challenge in cancer treatment.
- P-glycoprotein (P-gp) overexpression leads to drug efflux, reducing therapeutic efficacy.
- Nuclear-uptake nanodrug systems offer a strategy to bypass P-gp and enhance drug delivery.
Purpose of the Study:
- To develop a novel nanodrug delivery system for overcoming MDR in cancer.
- To design a system capable of coordinated intracellular and intranuclear drug delivery.
- To utilize DNA self-assembly and near-infrared (NIR) responsiveness for targeted drug delivery.
Main Methods:
- DNA self-assembly was employed to create a nanodrug system.
- Drug-loaded gold nanoparticles (nanodrugs) were assembled onto silver-gold nanorods (nanotrucks).
- Nanotrucks were functionalized with cell-specific aptamers and were NIR-responsive for controlled drug release.
Main Results:
- The nanodrug system demonstrated efficient accumulation of anticancer drugs within cancer cell nuclei.
- The system effectively bypassed P-gp efflux mechanisms, enhancing drug delivery.
- The size-photocontrollable nanodrug delivery system showed efficacy in killing drug-resistant cancer cells.
Conclusions:
- The developed nuclear-uptake nanodrug system shows promise for treating drug-resistant cancers.
- This approach offers a strategy to overcome MDR by targeting drug delivery to the nucleus.
- The combination of DNA self-assembly, aptamer targeting, and NIR responsiveness provides a versatile platform for cancer therapy.
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