The potential of gene therapy can be fully realized by successful synthesis of a smart cargo and co-delivery of inhibitory drugs. But use of cationic molecules for loading of oligo and polynucleotides and pre-mature leaching of small molecule drugs makes then unlikely to be successful. We have synthesized and biologically evaluated siNozyme-Am colloidal nanoparticles encompassing c-Myc antisense siRNA along with topo-II small molecule inhibitor, amonafide for therapy against human melanoma (Figure 1). As synthesized siNozymes nanoparticles were found to be stable spheroids with lamellar packing of loaded antisense oligonucleotide with small molecule drug. Markedly a higher cell population showed FITC tagged siRNA internalization for FITC-siNozyme treatment within 1h of incubation and showed &gt;75% growth inhibition even at smaller time point of ~24h post transfection and found to be significantly better than one of the commercial siRNA delivery agent used here. The co-loaded siNozyme particles with amonafide and siRNA were able to reduce the cell growth by ~90% even at 24h time point with non-significant improvement in cell growth even at higher time points of 48 and 72h. The basic achievement of this platform was to avoid coulombic interactions between siRNA and carrier assembly, use of a biomolecule Co-A derivative for making the nanoassembly and co-incorporation of small molecule drug of same working pathway to induce the effect. Because of its nanoparticle nature, siNozyme-Am assembly is expected to follow enhanced permeability and retention (EPR) path to enrich tumor in vivo. In future active targeting modalities can be added to this assembly. This unique combinatorial strategy through a cellular-friendly ‘nuclein’ type nano-assembly may provide a way ahead to the anti-sense therapy projects.

Pamitoyl-co-enzyme-A colloidal nanoparticles for transcriptional chemo-biologics therapy

255th National Meeting (2018)

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