Details

Autor(en) / Beteiligte

• Deng, Wei
• McKelvey, Kelly J
• Guller, Anna
• Fayzullin, Alexey
• Campbell, Jared M
• Clement, Sandhya
• Habibalahi, Abbas
• Wargocka, Zofia
• Liang, Liuen
• Shen, Chao
• Howell, Viive Maarika
• Engel, Alexander Frank
• Goldys, Ewa M

Titel

Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X‑ray-Induced Photodynamic Therapy for Rectal Cancer

Ist Teil von

• ACS central science, 2020-05, Vol.6 (5), p.715-726

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• In this work, we brought together two existing clinical techniques used in cancer treatmentX-ray radiation and photodynamic therapy (PDT), whose combination termed X-PDT uniquely allows PDT to be therapeutically effective in deep tissue. To this end, we developed mitochondrially targeted biodegradable polymer poly­(lactic-co-glycolic acid) nanocarriers incorporating a photosensitizer verteporfin, ultrasmall (2–5 nm) gold nanoparticles as radiation enhancers, and triphenylphosphonium acting as the mitochondrial targeting moiety. The average size of the nanocarriers was about 160 nm. Upon X-ray radiation our nanocarriers generated cytotoxic amounts of singlet oxygen within the mitochondria, triggering the loss of membrane potential and mitochondria-related apoptosis of cancer cells. Our X-PDT strategy effectively controlled tumor growth with only a fraction of radiotherapy dose (4 Gy) and improved the survival rate of a mouse model bearing colorectal cancer cells. In vivo data indicate that our X-PDT treatment is cytoreductive, antiproliferative, and profibrotic. The nanocarriers induce radiosensitization effectively, which makes it possible to amplify the effects of radiation. A radiation dose of 4 Gy combined with our nanocarriers allows equivalent control of tumor growth as 12 Gy of radiation, but with greatly reduced radiation side effects (significant weight loss and resultant death).