Journal
ACS APPLIED BIO MATERIALS
Volume 2, Issue 5, Pages 2162-2170Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.9b00146
Keywords
controlled drug delivery; polymer assembly; photoresponsive micelles; real-time cytotoxicity assays; water-soluble functional block copolymer
Funding
- Ministry of Science and Technology (MOST), Taiwan [MOST 105-2628-E-011-006-MY2, MOST 107-2221-E-011-041-MY3]
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An ultrasensitive light-responsive block copolymer, a combination of a multiarmed poly(ethylene glycol)-b-poly(caprolactone) polymer as a water-soluble element and maleimide-anthracene linkers as a photosensitive group, was successfully synthesized and rapidly self-assembled to form spherical micellar nanoparticles in aqueous media and phosphate-buffered saline. Their unique characteristics, such as extremely low critical micelle concentration, desirable micellar stability, well-controlled light-responsiveness, tailorable drug-loading content, and ultrasensitive light-induced drug release, make these micelles potential candidates for development of a more effective, safer drug delivery platform for cancer treatment. In vitro studies revealed that the drug-loaded micelles exhibited high structural stability in serum-containing media and very low toxicity toward normal and cancer cells under physiological conditions. Irradiation of cancer cells incubated with the drug-loaded micelles with ultraviolet light at 254 nm for only 10 s triggered rapid and complete release of the drug in the intracellular environment and induced strong antiproliferative/cytotoxic activity. Importantly, real-time cytotoxic assays and fluorescence imaging analysis further demonstrated that the drug-loaded micelles were rapidly taken up into the cytosol or nuclei of the cells, and subsequent ultraviolet exposure induced drug release and apoptotic cell death. Given their simplicity of design, high reliability, and performance, this new light-sensitive micelle may provide a promising route for developing a multifunctional therapeutic nanocarrier system.
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