Poly(amidoamine) Dendrimer-Gold Nanohybrids in Cancer Gene Therapy: A Concise Overview

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.

Glycoconjugate Nanoparticle-Based Systems in Cancer Immunotherapy: Novel Designs and Recent Updates

“…( 210 ). This group has pioneered the use of these dual nanoparticle constructs since the AuNP core imparts altered conformational properties to the ligand presentation on the dendrimer ( 211 ). The ingenious design is based on the use of both 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA) and 1,3-propane sultone in subsequent additions to a dendrimer to create a ligand for gadolinium based MRI imaging and a zwitterionic cap where siRNA can be ionically trapped facilitating its delivery ( Figure 8 ).…”

Next-generation engineered nanogold for multimodal cancer therapy and imaging: a clinical perspectives

“…Such gold nanocomplexes showed efficient delivery of siRNAs into the cells [ 170 ]. Despite using AuNPs alone, Au-dendrimers nanohybrids are also efficiently used to deliver nucleic acids for cancer gene therapy [ 171 ].…”

Dual-mode endogenous and exogenous sensitization of tumor radiotherapy through antifouling dendrimer-entrapped gold nanoparticles

“…In our earlier work, we demonstrate that dendrimer-entrapped gold nanoparticles (Au DENPs) can be used as an excellent gene vector simultaneously solving the high amine density-resulted cytotoxicity and low gene transfection efficiency 31 , 32 . This is due to the fact that the entrapped Au core particles within dendrimers help preserve the 3-dimensional conformation of PAMAM dendrimers for improved gene compaction, and likewise the entrapped Au cores require to be stabilized by a portion of dendrimer terminal amine to relieve the high density amine-induced cytotoxicity 33 . Previously, we have also shown that Au DENPs can be partially modified with acetamide 34 , polyethylene glycol (PEG) 35 , 36 , β-cyclodextrin 31 , 37 or zwitterion carboxybetaine acrylamide 38 for improved gene delivery.…”