Abstract |
Undesirable intracellular vesicular compartmentalization of anticancer drugs in cancer cells is a common cause of chemoresistance. Strategies aimed at circumventing this problem may improve chemotherapeutic efficacy. We report a novel photophysical strategy for controlled-disruption of vesicular sequestration of the anticancer drug doxorubicin (DOX). Single-walled carbon nanotubes (SWCNTs), modified with folate, were trapped in acidic vesicles after entering lung cancer cells. Upon irradiation by near-infrared pulsed laser, these vesicles were massively broken by the resulting photoacoustic shockwave, and the vesicle-sequestered contents were released, leading to redistribution of DOX from cytoplasm to the target-containing nucleus. Redistribution resulted in 12-fold decrease of the EC50 of DOX in lung cancer cells, and enhanced antitumor efficacy of low-dose DOX in tumor-bearing mice. Side effects were not observed. These findings provide insights of using nanotechnology to improve cancer chemotherapy, i.e. not only for drug delivery, but also for overcoming intracellular drug-transport hurdles.
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Authors | Aiping Chen, Chun Xu, Min Li, Hailin Zhang, Diancheng Wang, Mao Xia, Gang Meng, Bin Kang, Hongyuan Chen, Jiwu Wei |
Journal | Scientific reports
(Sci Rep)
Vol. 5
Pg. 15527
(Oct 20 2015)
ISSN: 2045-2322 [Electronic] England |
PMID | 26483341
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Drug Carriers
- Nanotubes, Carbon
- Doxorubicin
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Topics |
- Animals
- Antineoplastic Agents
(pharmacokinetics, pharmacology)
- Biological Transport
- Disease Models, Animal
- Doxorubicin
(pharmacokinetics, pharmacology)
- Drug Carriers
- Drug Delivery Systems
- Drug Resistance, Neoplasm
- Humans
- Intracellular Space
- Male
- Mice
- Nanotechnology
- Nanotubes, Carbon
(chemistry)
- Neoplasms
(drug therapy, pathology)
- Transport Vesicles
(metabolism)
- Xenograft Model Antitumor Assays
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