P07.08.A DEVISING AN EXOSOMES CONTROLLED-RELEASE HYDROGEL FOR GLIOBLASTOMA THERAPY

Abstract

Abstract BACKGROUND An efficient therapeutic method for glioblastoma hasn’t been founded. Nowadays, the combination of tumor surgery resection and chemoradiotherapy show limited outcomes even implanting a drug-loaded wafer on the tumor resection cavity during the surgery. Although Local drug delivery improves the adverse effects of intravenous chemotherapy drug injection, the low efficiency of drug transmembrane transportation still leads to poor therapeutic outcomes. Meanwhile, the stiff wafer is not able to perfectly match the irregular shape of the resection cavity. Recently, drug-loaded nanoparticles coated by tumor-derived exosomes applied in tumor-targeting drug delivery were frequently reported. The unique feature of tumor-homing, immune evasion of tumor-derived exosomes was used to improve the delivery efficiency, however, the therapeutic efficiency is weakened by liver filtration and the blood-brain barrier. MATERIAL AND METHODS For enhancing the therapeutic efficacy and compatibility of tumor resection cavity, in this project, a novel injectable hydrogel carrying DOX-loaded nanoparticles coated by tumor-derived exosomes, called Exo-DMSNs@CS, for intra-operative therapy of glioblastoma was devised. The doxorubicin-loaded nanoparticles encapsulated by tumor-derived exosomes (Exo-DMSNs) were integrated into body-temperature sensitive chitosan hydrogel, then injected into the tumor resection cavity and gelation along the shape. By passing the blood-brain barrier, the therapeutic efficacy can be improved by elevating the delivery efficiency induced by the released tumor-targeting Exo-DMSNs. RESULTS The hydrogel Exo-DMSNs@CS was successfully fabricated and contained features of thermosensitive, in vivo controlled releasing, in vitro tumor-targeting, and biocompatible. For simulating the scenario of intra-operative therapy, the Exo-DMSNs@CS was evaluated in the mice orthotopic GBM resection model. The decreased relapse speed and extended survival showed in the Exo-DMSNs@CS compared to DMSNs@CS demonstrated that the tumor-exosomes improve the prognosis of the mice. Moreover, the acceptable side effect was also confirmed. CONCLUSION The Eco-DMSNs@CS is suitable for therapy with better efficiency compared to traditional local drug delivery. This research provides a new strategy for glioblastoma patients and data support for similar product devising.