Vitro Co-Delivery of Decarbazine and Photosense loaded Exosome Nanocarrier for PDT based Combinational Therapy

Abstract

Exosomes are emerging as a natural nanocarrier having a potential to replace the synthetic nanoparticles in drug delivery applications due to their low immunogenicity and high biocompatibility. The objective of present study is to use exosomes as a nanocarrier for delivery of anticancer drugs during Photodynamic therapy (PDT) alone as well as in combination with the chemotherapy (combinational therapy).

In this study, exosomes were isolated and loaded with photosense (AlPc4) and decarbazine (DTIC, 5-3,3-(dimethyl-ltriazeno) imidazole-4-carboxamide) drug alone and in combination with 25nM and 250 nM concentrations. Further, these exosomes (blank as well loaded) were used during cytotoxicity test, PDT and combinational therapy on rhabdomyosarcoma (RD) cells.

Exosomes either loaded or unloaded showed no cellular toxicity (100% cell viability) on rhabdomyosarcoma (RD) cell culture, making them a biocompatible nanocarrier. On comparison, exosome mediated PDT showed more cell death alone then in combination with the chemotherapy (combinational therapy). Light inverted microscopic images showed cell swelling, and membrane rupture indicating the presence of necrosis during PDT and combinational therapy mediated cell death. Furthermore, expression analysis was carried out of five apoptosis related genes (CASP3, CASP9, P53, FOXO3a and PARP1) which shows downregulation in all treatment arms (cytotoxicity, PDT and combinational therapy).

On the basis of the results obtained, the absence of apoptotic mechanism is indicated during both PDT and combinational therapy in RD cells.