Application of mitochondrially targeted nanoconstructs to neo-adjuvant X-ray-induced photodynamic therapy for rectal cancer

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.