Functionalized Folate-Modified Graphene Oxide/PEI siRNA Nanocomplexes for Targeted Ovarian Cancer Gene Therapy

• Published in: Nanoscale research letters Vol. 15; no. 1; p. 57
• Main Authors: Wang, Yunfei, Sun, Guoping, Gong, Yingying, Zhang, Yuying, Liang, Xiaofei, Yang, Linqing
• Format: Journal Article
• Language: English
• Published: New York Springer US 06.03.2020; Springer Nature B.V; SpringerOpen
• Subjects: Atomic force microscopy; Cancer; Chemistry and Materials Science; Cholecystokinin; Confocal microscopy; Cytotoxicity; Electrophoresis; Evaluation; Folate; Folic acid; Fourier transforms; Gel electrophoresis; Gene therapy; Gene transfer; Graphene; Infrared spectroscopy; Light scattering; Lysosomal escape; Materials Science; Microscopy; Molecular Medicine; Nano Express; Nanochemistry; Nanoscale Science and Technology; Nanotechnology; Nanotechnology and Microengineering; Ovarian cancer; Ovarian carcinoma; Photon correlation spectroscopy; Scanning microscopy; siRNA; Stability analysis; Target; Toxicity; Tumors; GO; Target; Gene therapy; Folate; Ovarian cancer; Lysosomal escape
• ISSN: 1931-7573; 1556-276X; 1556-276X
• DOI: 10.1186/s11671-020-3281-7

Gene therapy is emerging as a valid method for the treatment of ovarian cancer, including small interfering RNA (siRNA). Although it is so powerful, few targeting efficient gene delivery systems seriously hindered the development of gene therapy. In this study, we synthesized a novel gene vector PEG-GO-PEI-FA by functionalized graphene oxide (GO), in which folic acid (FA) can specifically bind to the folate receptor (FR), which is overexpressed in ovarian cancer. Characterizations of the nanocomplexes were evaluated by dynamic light scattering (DLS), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). The siRNA condensation ability and stability were assessed by agarose gel electrophoresis. Cellular uptake efficiency and lysosomal escape ability in ovarian cancer cells were investigated by confocal laser scanning microscopy. Furthermore, cellular biosafety of the system and inhibitory of the siRNA tolerability were evaluated by CCK-8 assay. The size of the PEG-GO-PEI-FA nanocomplexes was 216.1 ± 2.457 nm, exhibiting mild cytotoxicity in ovarian cancer cells. With high uptake efficiency, PEG-GO-PEI-FA can escape from the lysosome rapidly and release the gene. Moreover, PEG-GO-PEI-FA/siRNA can effectively inhibit the growth of ovarian cancer cells. By and large, the PEG-GO-PEI-FA/siRNA may offer a promising strategy for siRNA delivery in the treatment of FR-positive ovarian carcinoma or similar tumors.