Oxygen-Carrying Polymer Nanoconstructs for Radiodynamic Therapy of Deep Hypoxic Malignant Tumors

Radiodynamic therapy (RDT) is an emerging non-invasive anti-cancer treatment based on the generation of the reactive oxygen species (ROS) at the lesion site following the interaction between X-rays and a photosensitizer drug (PS). The broader application of RDT is impeded by the tumor-associated hypoxia that results in low availability of oxygen for the generation of sufficient amounts of ROS. Herein, a novel nanoparticle drug formulation for RDT, which addresses the problem of low oxygen availability, is reported. It consists of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with a PS drug verteporfin (VP), and the clinically approved oxygen-carrying molecule, perfluorooctylbromide (PFOB). When triggered by X-rays (4 Gy), under both normoxic and hypoxic conditions, PLGA-VP-PFOB nanoconstructs (NCs) induced a significant increase of the ROS production compared with matching PLGA-VP nanoparticles. The RDT with NCs effectively killed similar to 60% of human pancreatic cancer cells in monolayer cultures, and almost completely suppressed the outgrowth of tumor cells in 2-weeks clonogenic assay. In a 3D engineered model of pancreatic cancer metastasis to the liver, RDT with NCs destroyed similar to 35% of tumor cells, demonstrating an exceptional efficiency at a tissue level. These results show that PLGA-VP-PFOB is a promising agent for RDT of deep-seated hypoxic tumors.

Automated summary

Radiodynamic therapy (RDT) is a promising non-invasive anti-cancer treatment that generates reactive oxygen species (ROS) through X-ray and a photosensitizer drug. A novel nanoparticle drug formulation for RDT, consisting of poly (lactic-co-glycolic acid) (PLGA) nanoparticles co-loaded with a photosensitizer drug verteporfin (VP) and an oxygen-carrying molecule, perfluorooctylbromide (PFOB), showed significant increase in ROS production under both normoxic and hypoxic conditions. RDT with these nanoparticles effectively killed pancreatic cancer cells and suppressed tumor cell outgrowth, demonstrating potential for treating deep-seated hypoxic tumors.