Michael Praveesuda L, Lam Yuen Ting, Hung Juichien, Tan Richard P, Santos Miguel, Wise Steven G
Faculty of Health and Medicine, School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia.
Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia.
Nanomaterials (Basel). 2021 Apr 29;11(5):1176. doi: 10.3390/nano11051176.
The rapid growth of nanoparticle-based therapeutics has underpinned significant developments in nanomedicine, which aim to overcome the limitations imposed by conventional therapies. Establishing the safety of new nanoparticle formulations is the first important step on the pathway to clinical translation. We have recently shown that plasma-polymerized nanoparticles (PPNs) are highly efficient nanocarriers and a viable, cost-effective alternative to conventional chemically synthesized nanoparticles. Here, we present the first comprehensive toxicity and biosafety study of PPNs using both established in vitro cell models and in vivo models. Overall, we show that PPNs were extremely well tolerated by all the cell types tested, significantly outperforming commercially available lipid-based nanoparticles (lipofectamine) used at the manufacturer's recommended dosage. Supporting the in vitro data, the systemic toxicity of PPNs was negligible in BALB/c mice following acute and repeated tail-vein intravenous injections. PPNs were remarkably well tolerated in mice without any evidence of behavioral changes, weight loss, significant changes to the hematological profile, or signs of histological damage in tissues. PPNs were tolerated at extremely high doses without animal mortality observed at 6000 mg/kg and 48,000 mg/kg for acute and repeated-injection regimens, respectively. Our findings demonstrate the safety of PPNs in biological systems, adding to their future potential in biomedical applications.
基于纳米颗粒的疗法的快速发展推动了纳米医学的重大进展，其旨在克服传统疗法所带来的局限性。确定新型纳米颗粒制剂的安全性是临床转化道路上的首要重要步骤。我们最近表明，等离子体聚合纳米颗粒（PPNs）是高效的纳米载体，是传统化学合成纳米颗粒可行且经济高效的替代品。在此，我们使用既定的体外细胞模型和体内模型，对PPNs进行了首次全面的毒性和生物安全性研究。总体而言，我们发现所有测试的细胞类型对PPNs的耐受性都非常好，明显优于以制造商推荐剂量使用的市售脂质基纳米颗粒（脂质体转染试剂）。支持体外数据的是，在急性和重复尾静脉注射后，PPNs在BALB/c小鼠中的全身毒性可忽略不计。PPNs在小鼠中耐受性非常好，没有任何行为变化、体重减轻、血液学特征显著变化或组织学损伤迹象的证据。在急性和重复注射方案中，分别在6000 mg/kg和48,000 mg/kg的极高剂量下，PPNs也具有耐受性，且未观察到动物死亡。我们的研究结果证明了PPNs在生物系统中的安全性，增加了它们在生物医学应用中的未来潜力。
