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

• Main Authors: Sandhya Clement, Anna Guller, Saabah B. Mahbub, Ewa M. Goldys
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Biomedicines
• Subjects: radiodynamic therapy; oxygen-carrying polymer nanoparticles; hypoxia; pancreatic cancer; 3D tumor model in vitro
• Online Access: https://www.mdpi.com/2227-9059/9/3/322

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 ⁓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 ~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.