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  • Mitochondrial-targeted photosensitizer-loaded folate-albumin nanoparticle for photodynamic therapy of cancer.

Mitochondrial-targeted photosensitizer-loaded folate-albumin nanoparticle for photodynamic therapy of cancer.

Nanomedicine : nanotechnology, biology, and medicine (2016-11-07)
Gantumur Battogtokh, Young Tag Ko
摘要

The objective of this study was to develop a mitochondria-targeted photosensitizer (PS) for photodynamic therapy (PDT). Herein, a porphyrin-derivative photosensitizer, pheophorbide-a (PheoA), was conjugated to carboxybutyltriphenylphosphonium (TPP) via a carbodiimide linkage to enhance mitochondrial targeting and TPP-PheoA conjugate was further loaded into folate-cholesteryl albumin (FA-chol-BSA) nanoparticles (NPs) to improve its biocompatibility. Cellular uptake results showed that TPP-PheoA and TPP-PheoA@FA-chol-BSA NPs were readily taken up by B16F10 and HeLa cells. Further in vitro studies exhibited that TPP-PheoA and its nanoparticle primarily accumulate in the mitochondria, greatly generate ROS, lead mitochondrial disruption and cell apoptosis, and have higher phototoxicity against cancer cells. In vivo bioimaging and the in vivo antitumor studies indicated that TPP-PheoA@FA-chol-BSA NP greatly accumulated in the tumor area and significantly suppress the tumor growth as compared to PheoA@FA-chol-BSA NP in tumor-bearing mice. Taken together, TPP-PheoA@FA-chol-BSA NP could be a promising mitochondria-targeted PS for image-guided PDT.

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Sigma-Aldrich
内消旋 -四苯基卟啉, BioReagent, suitable for fluorescence, ≥99.0% (HPLC)
Sigma-Aldrich
(4-羧丁基)三苯基溴化膦, 98%