期刊
NANOSCALE ADVANCES
卷 3, 期 20, 页码 5919-5927出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1na00427a
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology [20H04523, 21H0175301]
- Japanese Government (MEXT)
- Asahi Glass Foundation
- JSPS
- Indonesia Endowment Fund for Education (LPDP), Ministry of Finance of the Republic of Indonesia
- Ministry of Education and Culture of the Republic of Indonesia
- READYFOR Inc., Japan
- Shonan Health Innovation Park, Japan
- [JP16H06280]
- Grants-in-Aid for Scientific Research [20H04523] Funding Source: KAKEN
In photodynamic therapy, mitochondria are an important target for cancer therapy, but most clinically used photosensitizers have poor tumor accumulation and lack of mitochondria targeting ability. Using a nanocarrier platform, specific delivery of photosensitizers to mitochondria can be achieved, leading to significant in vivo antitumor activity. This study highlights the importance of a mitochondria-targeted nanocarrier system for enhancing the in vivo PDT efficacy in cancer therapy across different tumor types.
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.
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