Photoacoustic "nanobombs" fight against undesirable vesicular compartmentalization of anticancer drugs.
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.
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210093, China.|Nanjing University Hightech Institute at Suzhou, Suzhou, 215523, China.
Aiping
A
Chen
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210093, China.
Chun
C
Xu
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210093, China.|Nanjing University Hightech Institute at Suzhou, Suzhou, 215523, China.
Min
M
Li
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210093, China.
Hailin
H
Zhang
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210093, China.
Diancheng
D
Wang
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210093, China.
Mao
M
Xia
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210093, China.|Nanjing University Hightech Institute at Suzhou, Suzhou, 215523, China.
Gang
G
Meng
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210093, China.
Bin
B
Kang
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210093, China.
Hongyuan
H
Chen
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210093, China.|Nanjing University Hightech Institute at Suzhou, Suzhou, 215523, China.
Jiwu
J
Wei
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001692:Biological Transport; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D006801:Humans; D042541:Intracellular Space; D008297:Male; D051379:Mice; D036103:Nanotechnology; D037742:Nanotubes, Carbon / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D022161:Transport Vesicles / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D037742:Nanotubes, Carbon; D004317:Doxorubicin