Poly(amidoamine) Dendrimer-Gold Nanohybrids in Cancer Gene Therapy: A Concise Overview
Jin Li, Mingwu Shen, Xiangyang Shi
Abstract
Nonviral gene delivery has been considered as a powerful tool for cancer therapy because of its inherent advantages of nontoxicity, high specificity, and therapeutic efficacy. Successful cancer gene therapy mostly depends on the design of highly efficient and nontoxic vectors that can compress genetic materials and effectively deliver them to target cells. Dendrimers, in particular, poly(amidoamine) dendrimers with highly branched internal cavities and abundant surface amine groups, have been used as vectors for gene delivery but suffer problems of toxicity, low efficiency, and nonspecificity. Here, we summarize the updated progresses in the design of dendrimer-gold (Au) nanohybrids for improved gene delivery and cancer gene therapy by taking advantage of the unique properties of the integrated Au nanoparticles (AuNPs). In particular, the dendrimer-gold nanohybrids can be partially functionalized with acetyl, polyethylene glycol, and cyclodextrin to reduce their cytotoxicity; decorated with zwitterions to afford serum-enhanced gene delivery; and modified with targeting ligands to be rendered with the gene delivery specificity. A variety of genetic materials including plasmid DNA, small-interfering RNA, microRNA inhibitor, and immunoactivator have been delivered using the designed dendrimer-gold nanohybrids as vectors for effective gene therapy, immunotherapy, and combinational gene/photothermal therapy and gene/chemo therapy. We concisely overview the recent key developments of dendrimer-Au nanohybrids for improved cancer gene therapy and emphasize the role played by the AuNPs to boost the combinational therapy. The challenges and future perspectives regarding this particular area of research are also concisely discussed.