Applying photodynamics for radiotherapy-controlled drug delivery

Liposomes have been the most successful type of nanomedicine for cancer patients, playing a leading role in improving the tolerability of chemotherapeutics. However, to advance the success of liposomal drug delivery and cancer treatment, new approaches to physically trigger drug release in cancer tissues and increase the permeability of the protective cancer stroma are needed. To this end, photodynamics has been successfully harnessed for spatiotemporal-controlled drug release, alleviation of cancer desmoplasia, and improved efficacy of co-encapsulated or adjuvant chemotherapeutics. In this work, we present the adaptation of this approach for radiotherapy-controlled drug release, by functionalizing these liposomes with radiocatalytic- high-Z element-based nanomaterials. This strategy was explored in the context of chemo-radiation therapy for pancreatic cancer using in silico modeling, in vitro microtumor cultures, and orthotopic in vivo models of pancreatic cancer.