Lipoplex-based targeted gene therapy for the suppression of tumours with VEGFR expression by producing anti-angiogenic molecules
Journal
Journal of Nanobiotechnology
Journal Volume
18
Journal Issue
1
Date Issued
2020
Author(s)
Ho, S.-Y.
Chen, P.-R.
Chen, C.-H.
Tsai, N.-M.
Lin, Y.-H.
Chuang, C.-H.
Huang, X.-F.
Chan, Y.-L.
Liu, Y.-K.
Chung, C.-H.
Weng, S.-L.
Liao, K.-W.
Abstract
Background: 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. Results: 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. Conclusions: 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. ? 2020 The Author(s).
Subjects
Anti-angiogenesis; Gene therapy; LPPC; RBDV; VEGFR
SDGs
Other Subjects
Dermatology; Liposomes; Mammals; Molecules; Oncology; Proteins; Tumors; Angiogenic molecule; Growth suppressions; Lipo-peg-pei complexes; Receptor-binding domains; Targeting molecules; Therapeutic efficacy; Therapeutic transgene; Vascular endothelial growth factor-a; Gene therapy; angiogenesis inhibitor; deoxyribonuclease; immunoglobulin G1; lipoplex; macrogol; polyethyleneimine; RBDV protein; recombinant protein; unclassified drug; vasculotropin receptor; angiogenesis inhibitor; fusion protein; immunoglobulin Fc fragment; liposome; vasculotropin A; vasculotropin receptor; animal cell; animal experiment; animal model; animal tissue; antiangiogenic activity; antiangiogenic gene therapy; antineoplastic activity; Article; B16-F10 cell line; cancer gene therapy; controlled study; covalent bond; drug blood level; drug efficacy; drug targeting; enzyme degradation; female; gene targeting; human; human cell; in vitro study; in vivo study; male; maximum concentration; melanoma; molecularly targeted therapy; mouse; nanoencapsulation; nonhuman; nonviral gene delivery system; plasmid; protein expression; protein targeting; transgene; 3T3 cell line; allotransplantation; animal; biosynthesis; C57BL mouse; cell proliferation; chemistry; drug therapy; experimental melanoma; gene therapy; genetics; isolation and purification; metabolism; mortality; pathology; procedures; protein domain; survival rate; tumor cell line; 3T3 Cells; Angiogenesis Inhibitors; Animals; Cell Line, Tumor; Cell Proliferation; Genetic Therapy; Immunoglobulin Fc Fragments; Liposomes; Male; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Plasmids; Protein Domains; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Survival Rate; Transplantation, Homologous; Vascular Endothelial Growth Factor A
Type
journal article