Folate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy
Gene delivery systems have been developed on the basis of dendrimers and many other types of nanoparticle carriers, but few have been developed for head and neck squamous cell carcinomas (HNSCC). Herein, we describe the design and synthesis of fluorescently labeled, folic acid-decorated polyamidoamine (PAMAM) generation 4 (G4) dendrimer conjugates for HNSCC-targeted gene delivery. This delivery system comprises a dendrimer as the carrier that is conjugated with folic acid (FA) as HNSCC targeting moiety and imaging agents fluorescein isothiocyanate (FITC) or IRDye 800CW (NIR) for in vitro trafficking or bioimaging, respectively. By complexing with plasmid or siRNA, G4-FA/plasmid (or siRNA) significantly enhances gene transfection or knockdown efficiency in HNSCC cells. In a mouse xenograft model of HNSCC, this versatile G4-FA vector shows high biocompatibility, tumor targeting, high uptake, and sustained retention, making it a suitable platform for HNSCC gene therapy.
KeywordsDendrimer Targeted delivery Gene therapy Folate receptor Head and neck cancer
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