Abstract
The non-viral gene delivery system is an attractive alternative to cancer therapy. The clinical success of non-viral gene delivery is hampered by transfection efficiency and tumor targeting, which can be individually overcome by addition of functional modules such as cell penetration or targeting. Here, we first engineered the multifunctional gelatin/silica (GS) nanovectors with separately controllable modules, including tumor-targeting aptamer AGRO100, membrane-destabilizing peptide HA2, and polyethylene glycol (PEG), and then studied their bio-distribution and in vivo transfection efficiencies by contrast resonance imaging (CRI). The results suggest that the sizes and zeta potentials of multifunctional gelatin/silica nanovectors were 203–217 nm and 2–8 mV, respectively. Functional GS-PEG nanoparticles mainly accumulated in the liver and tumor, with the lowest uptake by the heart and brain. Moreover, the synergistic effects of tumor-targeting aptamer AGRO100 and fusogenic peptide HA2 promoted the efficient cellular internalization in the tumor site. More importantly, the combined use of AGRO100 and PEG enhanced tumor gene expression specificity and effectively reduced toxicity in reticuloendothelial system (RES) organs after intravenous injection. Additionally, low accumulation of GS-PEG was observed in the heart tissues with high gene expression levels, which could provide opportunities for non-invasive gene therapy.
Highlights
Gene delivery to cells can be accomplished by using viral and non-viral vectors
The use of viral vectors has been limited, leading to the evaluation and development of alternative vectors based on non-viral systems
The grafting of fusion peptides (Tat, R8, or HA2) onto GS NPs resulted in a synergistic effect on cellular internalization and transfection efficacy [22, 23]. These results indicated that these GS NPs have excellent properties as highly potent and non-toxic intracellular delivery systems, rendering them promising DNA vehicles to be used as non-viral gene delivery systems
Summary
Gene delivery to cells can be accomplished by using viral and non-viral vectors. To successfully translate the use of non-viral vectors from laboratories to clinics, numerous barriers such as transfection efficiency, tumor targeting, and blood clearance must be overcome to achieve efficient gene delivery [1]. The barriers can be individually overcome by the addition of functional modules such as conjugation of moieties for cell penetration or targeting. Some ligands such as cellpenetrating peptides Tat, fusogenic peptide HA2, and. The combination of multiple functional modules into a single nanocarrier can increase the intracellular delivery of many drugs, genes, and proteins, which might enhance their therapeutic efficacy [15,16,17]
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