Low-power and low-drug-dose photodynamic chemotherapy via the breakdown of tumor-targeted micelles by reactive oxygen species

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Tumor-targeted delivery of anticancer agents using nanocarriers has been explored to increase the therapeutic index of cancer chemotherapy. However, only a few nanocarriers are clinically available because the physiological complexity often compromises their ability to target, penetrate, and control the release of drugs. Here, we report a method which dramatically increases in vivo therapeutic drug efficacy levels through the photodynamic degradation of tumor-targeted nanocarriers. Folate-decorated poly(ethylene glycol)-polythioketal micelles are prepared to encapsulate paclitaxel and porphyrins. Photo-excitation generates reactive oxygen species within the micelles to cleave the polythioketal backbone efficiently and facilitate drug release only at the illuminated tumor site. Intravenous injection of a murine xenograft model with a low dose of paclitaxel within the micelles, one-milligram drug per kg (mouse), corresponding to an amount less than that of Taxol by one order of magnitude, induces dramatic tumor regression without any acute systemic inflammation responses or organ toxicity under low-power irradiation (55 mW cm(-2)) at 650 nm.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2018-09
Language
English
Article Type
Article
Keywords

NEAR-INFRARED LIGHT; BLOCK-COPOLYMER MICELLES; SINGLET-OXYGEN; POLYMERIC MICELLES; HYPERSENSITIVITY REACTIONS; INTRACELLULAR DELIVERY; ENDO/LYSOSOMAL ESCAPE; COMBINATION THERAPY; GENE DELIVERY; CELL LINES

Citation

JOURNAL OF CONTROLLED RELEASE, v.286, pp.240 - 253

ISSN
0168-3659
DOI
10.1016/j.jconrel.2018.07.046
URI
http://hdl.handle.net/10203/246043
Appears in Collection
MS-Journal Papers(저널논문)
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