Pigment epithelial-derived factor gene loaded novel COOH-PEG-PLGA-COOH nanoparticles promoted tumor suppression by systemic administration.
作者： Xiangrong Song , Ting Yu , Bei Xu , Lili He , Shan Xia
DOI: 10.2147/IJN.S97223
关键词: Cancer research 、 A549 cell 、 Systemic administration 、 Viral vector 、 In vivo 、 Transfection 、 Immunology 、 Genetic enhancement 、 Gene delivery 、 Medicine 、 PEDF
摘要: Anti-angiogenesis has been proposed as an effective therapeutic strategy for cancer treatment. Pigment epithelium-derived factor (PEDF) is one of the most powerful endogenous anti-angiogenic reagents discovered to date and PEDF gene therapy recognized a promising treatment option various tumors. There urgent need develop safe valid vector its systemic delivery. Herein, novel delivery system based on newly synthesized copolymer COOH-PEG-PLGA-COOH (CPPC) was developed in this study, which probably capable overcoming disadvantages viral vectors cationic lipids/polymers-based nonviral carriers. loaded CPPC nanoparticles (D-NPs) were fabricated by modified double-emulsion water-in-oil-in-water (W/O/W) solvent evaporation method. D-NPs with uniform spherical shape had relatively high drug loading (~1.6%), because introduced carboxyl group poly (D,L-lactide-co-glycolide) terminal enhanced interaction complexes. An excellent vitro antitumor effect found both C26 A549 cells treated D-NPs, levels dramatically elevated due successful transfection gene. also showed strong inhibitory proliferation human umbilical vein endothelial inhibited tumor-induced angiogenesis vivo alginate-encapsulated tumor cell assay. Further investigation, carried out subcutaneous model intravenous injection, demonstrated that could achieve significant activity sharply reduced microvessel density significantly promoted apoptosis. Additionally, hemolysis analysis serological biochemical revealed no obvious toxicity. All data indicated ideal might be widely used vectors.
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