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An effective in vivo mitochondria-targeting nanocarrier combined with a pi-extended porphyrin-type photosensitizer

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Title: An effective in vivo mitochondria-targeting nanocarrier combined with a pi-extended porphyrin-type photosensitizer
Authors: Satrialdi Browse this author
Takano, Yuta Browse this author
Hirata, Eri Browse this author
Ushijima, Natsumi Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Yamada, Yuma Browse this author →KAKEN DB
Issue Date: 21-Aug-2021
Publisher: Royal Society of Chemistry
Journal Title: Nanoscale advances
Volume: 3
Issue: 20
Start Page: 5919
End Page: 5927
Publisher DOI: 10.1039/d1na00427a
Abstract: A photochemical reaction mediated by light-activated molecules (photosensitizers) in photodynamic therapy (PDT) causes molecular oxygen to be converted into highly reactive oxygen species (ROS) that are beneficial for cancer therapy. As the active oxygen consumer and the primary regulator of apoptosis, mitochondria are known as an important target for optimizing PDT outcomes. However, most of the clinically used photosensitizers exhibited a poor tumor accumulation profile as well as lack of mitochondria targeting ability. Therefore, by applying a nanocarrier platform, mitochondria-specific delivery of photosensitizers can be materialized. The present research develops an effective mitochondria-targeting liposome-based nanocarrier system (MITO-Porter) encapsulating a pi-extended porphyrin-type photosensitizer (rTPA), which results in a significant in vivo antitumor activity. A single PDT treatment of the rTPA-MITO-Porter resulted in a dramatic tumor inhibition against both human and murine tumors that had been xenografted in a mouse model. Furthermore, depolarization of the mitochondrial membrane was observed, implying the damage of the mitochondrial membrane due to the photochemical reaction that occurred specifically in the mitochondria of tumor cells. The findings presented herein serve to verify the significance of the mitochondria-targeted nanocarrier system for advancing the in vivo PDT effectivity in cancer therapy regardless of tumor type.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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