항암약물(17AAG) 전달용 전기방사 나노섬유와 자살 유전자 치료를 위한 환원성 비바이러스 전달체 개발에 관한 연구

Abstract

Drug delivery system is used to improve the efficacy of drugs and reduce the side effects. In this study, 17AAG-loaded electrospun nanofibers and reducible non-viral carrier for suicide gene therapy were developed for the delivery of anti-cancer agents. First, electrospun polymeric nanofibers have been applied to tissue engineering, implants, wound dressing, and drug delivery systems. Among the various applications of nanofibers, we developed electrospun polymeric nanofibers for the drug delivery. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), anticancer drug, was loaded on the Poly(Ɛ-caprolactone) (PCL) and Poly(lactic-co-glycolic acid) (PLGA) nanofibers. The nanofibers were fabricated with both single nozzle and dual nozzles electrospinning procedures to compare properties such as the fiber morphology, loading efficiency and in vitro release profiles. The morphologies of both fibers were homogeneous and the fiber diameters were from 500 nm to 1000 nm. And the dual nozzles electrospun nanofibers showed a controlled in vitro release profile. As a result, electrospun 17AAG-loaded nanofibers could be promisimg local drug delivery systems for the treatment of tumor as implants. Second, for successful glioblastoma gene therapy, it is important to induce a specific gene expression in brain tumor tissues not in normal brain tissues. Previously, a novel glia and ischemia dual specific gene expression vector, pEpo-NI2-SV-TK, was constructed. And, enhanced gene expression and anti-cancer efficiency of pEpo-NI2-SV-TK with GCV treatment under hypoxia were demontrated. In addition, the 9-arginine-based reducible poly(oligo-D-arginine) (rPOA) is known as an efficient non-viral carrier that has high transfection efficiency and low cytotoxicity. In this study, the pEpo-NI2-SV-TK/rPOA polyplex with ganciclovir (GCV) combination systems improved the suicide gene therapy in the glioblastoma cells. The rPOA is an appropriate carrier for effective gene delivery into the brain and the pEpo-NI2-SV-TK/rPOA with GCV combination could be a superior suicide gene therapy for glioblastoma.