Multifunctional Platform Based on Cancer-Targeted Polymeric Nanoparticles for Enhanced Radiotherapy

Conventional radiotherapy is limited by off-target toxicity and the necessity of high-dose radiation. To address these challenges, we developed biodegradable PLGA-based radiosensitizing nanoparticles encapsulating metal nanoparticles and prodrugs, with lysyl oxidase (LOX) antibodies conjugated to the surface. The surface-bound LOX antibodies enhance targeting specificity toward the radiation-induced overexpressed LOX in the tumor microenvironments. Under gamma ray irradiation, metal NPs generate reactive oxygen species (ROS), which triggers the structural degradation of prodrugs. The PLGA based nanoparticles exhibited a uniform diameter with successful encapsulation of metal NPs and prodrugs. The biocompatibility of PLGA based nanoparticles was confirmed via live/dead assays using A549 3D tumor spheroids. Flow cytometry (Annexin V/PI) and confocal microscopy (TUNEL) analyses confirmed that the nanoplatform quantitatively and qualitatively induced cancer cell apoptosis. In conclusion, these multifunctional nanoparticles can maximize therapeutic efficacy and minimize side effects.