Antitumor therapeutic application of self-assembled RNAi-AuNP nanoconstructs: Combination of VEGF-RNAi and photothermal ablation

Abstract

Nucleic acid-directed self-assembly provides an attractive method to fabricate prerequisite nanoscale structures for a wide range of technological applications due to the remarkable programmability of DNA/RNA molecules. In this study, exquisite RNAi-AuNP nanoconstructs with various geometries were developed by utilizing anti-VEGF siRNA molecules as RNAi-based therapeutics in addition to their role as building blocks for programmed self-assembly. In particular, the anti-VEGF siRNA-functionalized AuNP nanoconstructs can take additional advantage of gold-nanoclusters for photothermal cancer therapeutic agent. A noticeable technical aspect of self-assembled RNAi-AuNP nanoconstructs in this study is the precise conjugation and separation of designated numbers of therapeutic siRNA onto AuNP to develop highly sophisticated RNA-based building blocks capable of creating various geometries of RNAi-AuNP nano-assemblies. The therapeutic potential of RNAi-AuNP nanoconstructs was validated in vivo as well as in vitro by combining heat generation capability of AuNP and anti-angiogenesis mechanism of siRNA. This strategy of combining anti-VEGF mechanism for depleting angiogenesis process at initial tumor progression and complete ablation of residual tumors with photothermal activity of AuNP at later tumor stage showed effective tumor growth inhibition and tumor ablation with PC-3 tumor bearing mice.

Engineering Nanoparticles for Targeted Delivery of Nucleic Acid Therapeutics in Tumor

“… 104 Son et al. 109 developed an exquisite RNAi-AuNP nanoconstruct with various geometries, which exhibited a precise conjugation and separation of a designated number of therapeutic siRNAs onto AuNP to create various geometries of RNAi-AuNP nanoassemblies, based on the hybridization between complementary nucleic acid base-pairing. Besides, using the property of mesenchymal stem cell (MSC) high affinity to bind arginine-glycine-aspartic (RGD) peptide, modifying RGD to dendrimer-entrapped AuNPs exhibited a highly efficient and specific gene delivery to stem cells.…”

RNAi technique, how far is it from pediatrics?

“…A typical example of such conditions are factors such as vascular endothelial growth factors (VEGF), epidermal growth factor receptor (EGFR) gene. In many malignant tumors, inhibition of expression of genes of such factors has become extremely important parts of anticancer treatment . The RNAi technique can reduce the expression of these factors sequentially.…”

“…In many malignant tumors, inhibition of expression of genes of such factors has become extremely important parts of anticancer treatment. 11,12 The RNAi technique can reduce the expression of these factors sequentially. Therefore, down-regulation of the expression of such factors applying the RNAi technique will become a very important part of the anticancer treatment.…”

New Targeted Gold Nanorods for the Treatment of Glioblastoma by Photodynamic Therapy

“…They have been employed in various biological applications including gene delivery, cell imaging, and photothermal therapy (PTT). These AuNRs are also familiar as drug delivery vehicles in cancer diagnostics and therapy [33][34][35][36][37][38][39][40][41][42][43]. The surface of the gold nanoparticles, in general, can be easily functionalized, thus establishing very stable conjugations [44].…”