期刊
BIOMACROMOLECULES
卷 15, 期 6, 页码 2224-2234出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm5003619
关键词
-
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2012R1A1A2005029, NRF-2013R1A2A2A04015914]
- Catholic University of Korea
In the study presented here, we developed a bioreducible biarmed methoxy poly(ethylene glycol)-(pheophorbide a)(2) (mPEG-(ss-PhA)(2)) conjugate for cancer-cell-specific photodynamic therapy (PDT). PhA molecules were chemically conjugated with biarmed linkages at one end of the mPEG molecule via disulfide bonds. Under aqueous conditions, the amphiphilic mPEG-(ss-PhA)(2) conjugate self-assembled to form core shell-structured nanoparticles (NPs) with good colloidal stability. The mPEG-(ss-PhA)(2) NPs exhibited intramolecular and intermolecular self-quenching effects that enabled the NPs to remain photoinactive in a physiological buffer. However, the dissociation of the NP structure was effectively induced by the cleavage of the disulfide bonds in response to intracellular reductive conditions, triggering the rapid release of PhA molecules in a photoactive form. In cell-culture systems, in addition to significant phototoxicity and intracellular uptake, we observed that the dequenching processes of PhA in the mPEG-(ss-PhA)(2) NPs highly depended on the expression of intracellular thiols and that supplementation with glutathione monoethylester facilitated more rapid PhA release and enhanced the PhA phototoxicity. These findings suggest that the bioreducible activation mechanism of mPEG-(ss-PhA)(2) NPs in cancer cells can maximize the cytosolic dose of active photosensitizers to achieve high cytotcodcity, thereby enhancing the treatment efficacy of photodynamic cancer treatment.
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