Abstract
The high efficiency and specificity of gene therapy are mainly ascribed to the excellent transfection ability of the gene carrier. Non-viral polymer vectors have attracted extensive attention because of their low cytotoxicity and outstanding genetic loading capacity compared with viral vectors. For safe and efficient transfection of nuclear acids, here we report a novel gene delivery system, dendrimer-entrapped gold nanoparticles modified with a folate-conjugated poly (ethylene glycol) (Au DENPs-PEG-FA), possessing superior gene transfection efficiency than that of partially hydrophilic methoxy poly(ethylene glycol) (mPEG)-modified dendrimer-entrapped gold nanoparticles (Au DENPs-mPEG). The prepared Au DENPs-PEG-FA were well characterized, and our data revealed that the vector showed good cytocompatibility. Additionally, the quantification of inflammatory cytokines detected by qRT-PCR showed that the vectors displayed low innate immune response. The efficiency of nucleic acid (encoding enhanced green fluorescent protein (EGFP) and luciferase (Luc) reporter) transfection evaluated via flow cytometry and confocal microscopic imaging suggested that the Au DENPs-PEG-FA were able to transfect nucleic acid into HeLa cells with enhanced transfection efficiency. Furthermore, the existence of FA rendered the Au DENPs with excellent targeting performance via FA receptor-ligand binding interaction. The designed Au DENPs-PEG-FA with low immunogenicity and enhanced gene transfection efficiency may hold a great promise to be a superior vector for gene therapy.
Highlights
Cancer represents a disease with high incidence and is the main research object for gene therapy
According to our previous studies,[19,20] we successfully prepared Au DENPs-PEG-folic acid (FA) by using generation 5 (G5).NH2 dendrimers as a template, and Au DENPs-methoxy poly(ethylene glycol) (mPEG) were synthesized as control (Scheme 1)
According to the UV/Vis spectrophotometry, the absorption peak at 520 nm for two materials can be assigned to the surface plasmon resonance (SPR) band of Au NPs, con rming the successful formation of
Summary
Cancer represents a disease with high incidence and is the main research object for gene therapy. Nonviral transfection is more advantageous and attractive Synthetic carriers such as polycations have been proposed as efficient and safe alternative to viral systems for gene delivery.[3,4] Due to the high cytotoxicity, the surface of polycations, such as polyamidoamine (PAMAM) dendrimers, need to be modi ed. Jevprasesphant et al.[8] and Luo et al.[9] have proved that modi cation of PEG can reduce the cytotoxicity of PAMAM vector and signi cantly improve the efficiency of gene transfection. Apart from cytotoxicity, another side effect of unwanted activation of the immune system limit the further applications of nanomaterials in gene therapy. The functionalized dendrimers modi ed with FA are low immunogenic and can realize the targeted gene delivery to transfer both EGFP gene and Luc reporter gene to HeLa cells
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