Department of Physiology, School of Medical Sciences, University of Sydney, Sydney, Australia.
Charles Perkins Centre, University of Sydney, Sydney, Australia.
Sci Rep. 2020 Jul 30;10(1):12836. doi: 10.1038/s41598-020-69591-x.
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 µg/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.
多功能纳米载体 (MNCs) 有望通过将多种分子结合到单个纳米结构中,增强治疗剂的主动靶向并促进新的联合治疗,从而改善治疗效果。然而,目前临床批准使用的纳米载体平台仍然只能携带单一的治疗剂。由于合成更复杂的 MNCs 的复杂性和成本不断增加,这一直是临床转化途径中的主要技术障碍。在这里,我们表明,在反应性气体放电中合成的等离子体聚合纳米颗粒 (PPN) 可以在简单且具有成本效益的过程中结合并有效传递多种治疗性货物,该过程与可扩展的商业生产兼容。与携带更高剂量 siRNA 的商业平台(6.25 nM)相比,以极低浓度(0.04 nM)递送针对血管内皮生长因子 (siVEGF) 的 siRNA 可显著降低难以转染的细胞中 VEGF 的表达。以较低剂量(<100 µg/kg)携带 siVEGF 和标准护理紫杉醇的 PPN(PPN-Dual)组合协同调节了小鼠原位乳腺癌肿瘤的微环境,并显著抑制了肿瘤生长。我们提出 PPN 作为一种新的治疗药物传递纳米材料,无需额外的湿化学和纯化步骤,即可在任何实验室环境中轻松进行功能化。
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