Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome

Abstract

Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to the tumor even in the presence of anti-viral Nabs could be gold nanoparticles able to transfer DNA molecules. However, the ability of these nanoparticles to carry large DNA molecules, such as an oncolytic adenovirus genome, has not been studied. In this work, gold nanoparticles were functionalized with different amounts of polyethylenimine to transfer in a safe and efficient manner a large oncolytic virus genome. Their transfer efficacy and final effect of the oncolytic virus in cancer cells are studied. For each synthesized nanoparticle, (a) DNA loading capacity, (b) complex size, (c) DNA protection ability, (d) transfection efficacy and (e) cytotoxic effect were studied. We observed that small gold nanoparticles (70–80 nm in diameter) protected DNA against nucleases and were able to transfect the ICOVIR-15 oncolytic virus genome encoded in pLR1 plasmid. In the present work, efficient transgene RNA expression, luciferase activity and viral cytopathic effect on cancer cells are reported. These results suggest gold nanoparticles to be an efficient and safe vector for oncolytic adenovirus genome transfer.

Oncolytic Virotherapy: A New Paradigm in Cancer Immunotherapy

“…AuNPs are widely used in oncolytic viral therapy, facilitating the access of DNA to the tumors despite the presence of antibodies [207]. A particle containing Ad coated with micelles and conjugated with paclitaxel was designed and demonstrated high efficiency against tumors [208].…”

Horseradish Peroxidase-Functionalized Gold Nanoconjugates for Breast Cancer Treatment Based on Enzyme Prodrug Therapy

“…29,30 Moreover, their synthesis is straightforward with tunable size (1-200 nm) [31][32][33] and shape (ie, spherical, rods, star nanoparticles, etc.). 34 Further versatility is given by ready surface functionalization with biomolecules, such as enzymes, 35,36 oligonucleotides, 37,38 proteins, 39,40 drugs, [41][42][43] and its potential incorporation in Janus-like ensembles for advanced applications. [44][45][46][47] In turn, gold nanoparticles hold special interest as enzyme nanocarriers.…”