The anti-angiogenic fusion protein RBDV-IgG1 Fc (RBDV), which comprises the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A), has shown antitumour effects by reducing angiogenesis in vivo. This study used the cationic lipoplex lipo-PEG-PEI-complex (LPPC) to simultaneously encapsulate both the RBDV targeting protein and the RBDV plasmid (pRBDV) without covalent bonds to assess VEGFR targeting gene therapy in mice with melanoma in vivo. LPPC protected the therapeutic transgene from degradation by DNase, and the LPPC/RBDV complexes could specifically target VEGFR-positive B16-F10 cells both in vitro and in vivo. With or without RBDV protein-targeting direction, the pRBDV-expressing RBDV proteins were expressed and reached a maximal concentration on the 7th day in the sera after transfection in vivo and significantly elicited growth suppression against B16-F10 melanoma but not IgG1 control proteins. In particular, LPPC/pRBDV/RBDV treatment with the targeting molecules dramatically inhibited B16-F10 tumour growth in vivo to provide better therapeutic efficacy than the treatments with gene therapy with IgG1 protein targeting or administration of a protein drug with RBDV. The simultaneous combination of the LPPC complex with pRBDV gene therapy and RBDV protein targeting might be a potential tool to conveniently administer targeted gene therapy for cancer therapy.

中文翻译：

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基于脂质复合体的靶向基因疗法，通过产生抗血管生成分子来抑制具有VEGFR表达的肿瘤

包含血管内皮生长因子-A（VEGF-A）受体结合域的抗血管生成融合蛋白RBDV-IgG1 Fc（RBDV）已通过减少体内血管生成而表现出抗肿瘤作用。这项研究使用阳离子脂质复合物脂质-PEG-PEI复合物（LPPC）同时包裹没有共价键的RBDV靶向蛋白和RBDV质粒（pRBDV）来评估体内黑色素瘤小鼠的VEGFR靶向基因治疗。LPPC保护治疗性转基因免于被DNase降解，并且LPPC / RBDV复合物可以在体内外特异性靶向VEGFR阳性B16-F10细胞。有或没有RBDV蛋白靶向方向，体内转染后，表达pRBDV的RBDV蛋白在血清中第7天表达并达到最大浓度，并显着引起针对B16-F10黑色素瘤的生长抑制，但不引起IgG1对照蛋白的生长抑制。特别是，用靶向分子进行的LPPC / pRBDV / RBDV处理可显着抑制体内B16-F10肿瘤的生长，从而提供比采用IgG1蛋白靶向的基因治疗或用RBDV施用蛋白药物的治疗更好的治疗效果。LPPC复合物与pRBDV基因治疗和RBDV蛋白靶向的同时结合可能是方便地将靶向基因治疗用于癌症治疗的潜在工具。用靶向分子的LPPC / pRBDV / RBDV处理可显着抑制体内B16-F10肿瘤的生长，从而比以IgG1蛋白靶向的基因治疗或以RBDV施用蛋白药物的治疗提供更好的治疗效果。LPPC复合物与pRBDV基因治疗和RBDV蛋白靶向的同时结合可能是方便地将靶向基因治疗用于癌症治疗的潜在工具。用靶向分子的LPPC / pRBDV / RBDV处理可显着抑制体内B16-F10肿瘤的生长，从而比以IgG1蛋白靶向的基因治疗或以RBDV施用蛋白药物的治疗提供更好的治疗效果。LPPC复合物与pRBDV基因治疗和RBDV蛋白靶向的同时结合可能是方便地将靶向基因治疗用于癌症治疗的潜在工具。