Radiodynamic therapy using tat peptide‐targeted verteporfin‐encapsulated plga nanoparticles

Abstract

Radiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well‐tolerated dose of highenergy X‐rays. This enables greater tissue penetration to allow non‐invasive treatment of large, deep‐seated tumors. We report here the design and testing of a drug delivery system for RDT that is intended to enhance intra‐ or peri‐nuclear localization of the photosensitizer, leading to DNA damage and resulting clonogenic cell kill. This comprises a photosensitizer (Verteporfin, VP) incorporated into poly (lactic‐co‐glycolic acid) nanoparticles (PLGA NPs) that are surface‐functionalized with a cell‐penetrating HIV trans‐activator of transcription (TAT) peptide. In addition to a series of physical and photophysical characterization studies, cytotoxicity tests in pancreatic (PANC‐1) cancer cells in vitro under 4 Gy X‐ray exposure from a clinical 6 MV linear accelerator (LINAC) showed that TAT targeting of the nanoparticles markedly enhances the effectiveness of RDT treatment, particularly when assessed by a clonogenic, i.e., DNA damage‐mediated, cell kill.