Biochemistry Laboratory, Animal Facility, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow 226028, Uttar Pradesh, India.
Water Analysis Laboratory, Nanotherapeutics and Nanomaterials Toxicology Group, CSIR-Indian Institute of Toxicology Research, (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
J Pharm Sci. 2019 May;108(5):1872-1889. doi: 10.1016/j.xphs.2018.12.021. Epub 2019 Jan 5.
In biological system, the interaction between nanoparticles (NPs) and serum biomolecules results in the formation of a dynamic corona of different affinities. The formed corona enriched with opsonin protein is recognized by macrophages and immune effector cells, resulting in rapid clearance with induced toxicity. Hence, to reduce corona genesis, surface-engineered ZnO (c-ZnO) NPs were in situ synthesized using a polyacrylamide-grafted guar gum (PAm-g-GG) polymer that provided surface neutrality to the NPs. Furthermore, we studied the characteristics of the corona formed onto uncapped anionic ZnO (bared ZnO [b-ZnO]) NPs and c-ZnO NPs by serum incubation. The result shows that b-ZnO NPs were wrapped with a high amount of serum proteins, particularly opsonin (IgG and complement), compared with c-ZnO NPs. These corona findings helped us substantially in interpretation of in vivo biokinetics studies. The in vivo study was accomplished by oral administration of NPs to Swiss mice at doses of 300 and 2000 mg/kg body weight. The studies performed on the cellular uptake, intracellular particle distribution, cytotoxicity, and pharmacokinetics of NPs indicated that b-ZnO NPs experienced higher immune cell recognition, hepatic inflammation, and resultant rapid clearance from the system, unlike c-ZnO NPs. Thus, capping of NPs by a neutral polymer has provided limited binding sites for undesired proteins around NPs, which limits immune system activation.
在生物系统中，纳米颗粒（NPs）与血清生物分子之间的相互作用导致形成具有不同亲和力的动态冠层。形成的富含调理蛋白的冠层被巨噬细胞和免疫效应细胞识别，导致诱导毒性的快速清除。因此，为了减少冠层的形成，使用接枝有聚丙烯酰胺的瓜尔胶（PAm-g-GG）聚合物原位合成了表面工程化的氧化锌（c-ZnO） NPs，该聚合物为 NPs 提供了表面中性。此外，我们研究了血清孵育后在未封端的阴离子氧化锌（裸 ZnO [b-ZnO]）NPs 和 c-ZnO NPs 上形成的冠层的特性。结果表明，与 c-ZnO NPs 相比，b-ZnO NPs 被大量的血清蛋白包裹，特别是调理素（IgG 和补体）。这些冠层研究结果极大地帮助我们解释了体内生物动力学研究。通过给瑞士小鼠口服 NPs 来完成体内研究，剂量分别为 300 和 2000 mg/kg 体重。对 NPs 的细胞摄取、细胞内颗粒分布、细胞毒性和药代动力学的研究表明，b-ZnO NPs 经历了更高的免疫细胞识别、肝炎症和由此导致的从系统中快速清除，而 c-ZnO NPs 则不然。因此，中性聚合物对 NPs 的封端为 NPs 周围不需要的蛋白质提供了有限的结合位点，从而限制了免疫系统的激活。
