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Photoacoustic "nanobombs" fight against undesirable vesicular compartmentalization of anticancer drugs.

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.
AuthorsAiping Chen, Chun Xu, Min Li, Hailin Zhang, Diancheng Wang, Mao Xia, Gang Meng, Bin Kang, Hongyuan Chen, Jiwu Wei
JournalScientific reports (Sci Rep) Vol. 5 Pg. 15527 (Oct 20 2015) ISSN: 2045-2322 [Electronic] England
PMID26483341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Drug Carriers
  • Nanotubes, Carbon
  • Doxorubicin
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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