Nuclear targeted x-ray activated photodynamic therapy: a solution to treat pancreatic cancer (Conference Presentation)

Abstract

Pancreatic cancer is a highly lethal malignancy and a leading cause of cancer death in the world. Patients are either treated by surgery or by means of radiation therapy or by means of chemotherapy or by combining radiation and chemotherapy together depends upon the status of the pancreatic cancer. All these current treatments have limited efficacy as well as significant toxicity. Photodynamic therapy (PDT) is relatively free from side effects, but it is currently not applicable to pancreatic cancer due to its location in deep tissue. Herein, we developed a PDT system which uses poly (D, L-lactide-co-glycolide) (PLGA) polymeric nanoparticles incorporating a photosensitizer, verteporfin, to generate cytotoxic reactive oxygen species (ROS) by X-ray radiation of 6 MeV. The use of X-ray as the source of energy to trigger verteporfin avoids the limitation of poor penetration depth in conventional PDT. In addition, TAT peptide, a targeting moiety conjugated to the surface of the PLGA nanoconstructs facilitates the targeting of nanoparticles towards the nucleus of the cancer cells. The physiochemical characterisation as well as ROS generation capabilities of the nanoconstructs were studied under 6 MeV X-rays. We believe that the X-ray-induced ROS generation from Verteporfin molecules may be due to Cerenkov radiation (CR) and/or generation of energetic electron by the 6 MeV X-rays which then produce a cascade of ROSs. The cellular experiments carried out in Panc-1 cancer cell line suggest that an improved therapeutic effects can be achieved with the nanoconstructs triggered with X-ray radiation, compared with radiation alone.