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we developed mitochondrially targeted biodegradable polymerpoly(lactic-co-glycolic acid) nanocarriers incorporating a photosensitiser verteporfin, ultrasmall (2-5 nm) gold nanoparticles as radiation enhancers and triphenylphosphonium acting as the mitochondrial targeting moiety. 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 tumour growth with only a fraction of radiotherapy dose (4 Gy) and improved the survival rate of a mouse model bearing colorectal cancer cells. It may offer a paradigm-shifting treatment alternative for patients who need neoadjuvant radiotherapy but wish to avoid long term detrimental effect on functional outcome by undergoing X-PDT using only a fraction of the conventional radiotherapy.
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Wei Deng, Kelly McKelvey, Anna Guller, Jared Campbell, Sandhya Clement, Abbas Habibalahi, Ewa Goldys, "Application of mitochondrially targeted nanoconstructs to neo-adjuvant X-ray-induced photodynamic therapy for rectal cancer," Proc. SPIE 11628, Mechanisms and Techniques in Photodynamic Therapy and Photobiomodulation, 116280G (5 March 2021); https://doi.org/10.1117/12.2578073