Gwak So-Jung, Lee Jeoung Soo
Department of Bioengineering, Drug Design, Development and Delivery (4D) Laboratory, Clemson University, Clemson, SC 29634-0905, USA.
Department of Chemical Engineering, Wonkwang University, 460, Iksandae-ro, Iksan, Jeonbuk 54538, Korea.
Nanomaterials (Basel). 2019 Apr 8;9(4):573. doi: 10.3390/nano9040573.
Spinal cord tumors (SCT) are uncommon neoplasms characterized by irregular growth of tissue inside the spinal cord that can result in non-mechanical back pain. Current treatments for SCT include surgery, radiation therapy, and chemotherapy, but these conventional therapies have many limitations. Suicide gene therapy using plasmid encoding herpes simplex virus-thymidine kinase (pHSV-TK) and ganciclovir (GCV) has been an alternative approach to overcome the limitations of current therapies. However, there is a need to develop a carrier that can deliver both pHSV-TK and GCV for improving therapeutic efficacy. Our group developed a cationic, amphiphilic copolymer, poly (lactide-co-glycolide) -graft-polyethylenimine (PgP), and demonstrated its efficacy as a drug and gene carrier in both cell culture studies and animal models. In this study, we evaluated PgP as a gene carrier and demonstrate that PgP can efficiently deliver reporter genes, pGFP in rat glioma (C6) cells in vitro, and pβ-gal in a rat T5 SCT model in vivo. We also show that PgP/pHSV-TK with GCV treatment showed significantly higher anticancer activity in C6 cells compared to PgP/pHSV-TK without GCV treatment. Finally, we demonstrate that PgP/pHSV-TK with GCV treatment increases the suicide effect and apoptosis of tumor cells and reduces tumor size in a rat T5 SCT model.
脊髓肿瘤（SCT）是一种罕见的肿瘤，其特征是脊髓内组织不规则生长，可导致非机械性背痛。目前SCT的治疗方法包括手术、放射治疗和化疗，但这些传统疗法有许多局限性。使用编码单纯疱疹病毒胸苷激酶（pHSV-TK）和更昔洛韦（GCV）的质粒进行自杀基因治疗是克服当前疗法局限性的一种替代方法。然而，需要开发一种能够同时递送pHSV-TK和GCV的载体，以提高治疗效果。我们的研究小组开发了一种阳离子两亲共聚物，聚（丙交酯-共-乙交酯）-接枝-聚乙烯亚胺（PgP），并在细胞培养研究和动物模型中证明了其作为药物和基因载体的功效。在本研究中，我们评估了PgP作为基因载体的效果，并证明PgP能够在体外将报告基因pGFP有效地递送至大鼠胶质瘤（C6）细胞中，在体内大鼠T5脊髓肿瘤模型中递送pβ-半乳糖苷酶基因。我们还表明，与未用GCV处理的PgP/pHSV-TK相比，用GCV处理的PgP/pHSV-TK在C6细胞中显示出显著更高的抗癌活性。最后，我们证明，在大鼠T5脊髓肿瘤模型中，用GCV处理的PgP/pHSV-TK增加了肿瘤细胞的自杀效应和凋亡，并减小了肿瘤大小。
