Journal
NANO LETTERS
Volume 15, Issue 1, Pages 457-463Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nl503777s
Keywords
Nuclear uptake; photocontrollable size; drug-resistant cancer therapy; cell-targeted delivery; aptamer
Categories
Funding
- American Chemical Society, Division of Analytical Chemistry Fellowship - Society for Analytical Chemists of Pittsburgh
- National Key Scientific Program [2011YQ03012412]
- National Institutes of Health [GM079359, CA133086]
- NATIONAL CANCER INSTITUTE [R01CA133086] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM079359] Funding Source: NIH RePORTER
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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 silvergold 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.
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