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Plasma polymerized nanoparticles effectively deliver dual siRNA and drug therapy in vivo

Abstract

Multifunctional nanocarriers (MNCs) promise to improve therapeutic outcomes by combining multiple classes of molecules into a single nanostructure, enhancing active targeting of therapeutic agents and facilitating new combination therapies. However, nanocarrier platforms currently approved for clinical use can still only carry a single therapeutic agent. The complexity and escalating costs associated with the synthesis of more complex MNCs have been major technological roadblocks in the pathway for clinical translation. Here, we show that plasma polymerized nanoparticles (PPNs), synthesised in reactive gas discharges, can bind and effectively deliver multiple therapeutic cargo in a facile and cost-effective process compatible with up scaled commercial production. Delivery of siRNA against vascular endothelial growth factor (siVEGF) at extremely low concentrations (0.04 nM), significantly reduced VEGF expression in hard-to-transfect cells when compared with commercial platforms carrying higher siRNA doses (6.25 nM). PPNs carrying a combination of siVEGF and standard of care Paclitaxel (PPN-Dual) at reduced doses (< 100 microg/kg) synergistically modulated the microenvironment of orthotopic breast tumors in mice, and significantly reduced tumor growth. We propose PPNs as a new nanomaterial for delivery of therapeutics, which can be easily functionalised in any laboratory setting without the need for additional wet-chemistry and purification steps.

Type Journal
ISBN 2045-2322 (Electronic) 2045-2322 (Linking)
Authors Michael, P.; Lam, Y. T.; Filipe, E. C.; Tan, R. P.; Chan, A. H. P.; Lee, B. S. L.; Feng, N.; Hung, J.; Cox, T. R.; Santos, M.; Wise, S. G.
Responsible Garvan Author A/Prof Thomas Cox
Publisher Name Scientific Reports
Published Date 2020-07-31
Published Volume 10
Published Issue 1
Published Pages 12836
Status Published in-print
DOI 10.1038/s41598-020-69591-x
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/32732927