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 cytotoxicity, thereby enhancing the treatment efficacy of photodynamic cancer treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.