Multi-functional self-assembled nanoparticles for pVEGF-shRNA loading and anti-tumor targeted therapy.
Although RNA interference (RNAi) technology shows great potential in cancer treatment, the tumor target delivery and sufficient cytosolic transport of RNAi agents are still the main obstacles for its clinical applications. Herein, we report a functional supramolecular self-assembled nanoparticle vector for RNAi agent loading and tumor target therapy. Molecular block adamantane-grafted poly(ethylene glycol) (Ad-PEG) was modified with epidermal growth factor receptor (EGFR)-specific binding ligand GE11 or pH-sensitive fusogenic peptide GALA and then used for self-assembly with cyclodextrin-grafted branched polyethylenimine (CD-PEI), adamantane-grafted polyamidoamine dendrimer (Ad-PAMAM), and plasmid DNA containing a small hairpin RNA expression cassette against vascular endothelial growth factor (VEGF) into functional DNA-loaded supramolecular nanoparticles (GE11&GALA-pshVEGF@SNPs) based on molecular recognition and charge interaction. These functional peptides facilitated the target cell binding, internalization, and endosomal escape of GE11&GALA-pshVEGF@SNPs, resulting in increased reporter gene expression and efficient targeted gene silencing. The systemic delivery of the GE11&GALA-pshVEGF@SNPs can efficiently downregulate the intratumoral VEGF protein levels, reduce blood vessel formation, and significantly inhibit A549 xenograft tumor growth. These results reveal the potential of these multifunctional self-assembled nanoparticles as a nucleic acid drug delivery system for the treatment of lung cancer.
['Lu|Sai|S|', 'Bao|Xiao|X|', 'Hai|Wangxi|W|', 'Shi|Sanyuan|S|', 'Chen|Yuetan|Y|', 'Yu|Qianru|Q|', 'Zhang|Maxin|M|', 'Xu|Yuhong|Y|', 'Peng|Jinliang|J|']
D000072283:A549 Cells D000218:Adamantane D000818:Animals D004247:DNA D005260:Female D020868:Gene Silencing D006801:Humans D008819:Mice, Nude D058990:Molecular Targeted Therapy D053758:Nanoparticles D009369:Neoplasms D009389:Neovascularization, Pathologic D010455:Peptides D010957:Plasmids D011108:Polymers D034741:RNA, Small Interfering D047368:Tumor Burden D042461:Vascular Endothelial Growth Factor A
Targeted therapy pH-sensitive fusogenic peptide GALA Multifunctional self-assembled nanoparticle EGFR-binding peptide GE11 shRNA