Cui Teng, Ma Yu, Yang Jian-Yong, Liu Shang, Wang Zhenzhen, Zhang Fenfen, Wang Jing, Cai Ting, Dong Lei, Hong Jin, Qian Hai, Zhang Can, Ding Ya
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China.
Nanoscale. 2021 Mar 21;13(11):5883-5891. doi: 10.1039/d1nr00426c. Epub 2021 Mar 16.
The discovery of protein corona (PC) formed on the surface of nanomaterials has promoted research on PC regulation to guide the biological behavior of nanomaterials in vivo. Different from changing the size, shape, and surface charge of nanoparticles, we propose to control the nature of PC by adjusting the molecular weight of low molecular weight polyethylene glycol (LMW PEG, not more than 1000 Da) on the surface of the particles. After excluding the influence of physicochemical factors of PEGylated gold nanoparticles (GNPs), different proteins on the surface of PEGylated GNPs were separated and identified after incubation with human plasma. It is noted that GNP-550 bearing PEG chains of 550 Da absorbed more transferrin responsible for tumor targeting than the other two particles, i.e., GNP-350 and GNP-1000. To validate our speculation, doxorubicin (Dox) was inserted between GNPs and PEGs to explore the cellular and animal studies of Dox-conjugated GNPs. Interestingly, Dox-containing Conj-550 also showed the highest intracellular uptake, cytotoxicity, and apoptosis against HepG2 cells, as well as the best tumor targeting effect and antitumor efficacy in Heps-bearing mice. This protein corona-guided tumor targeting therapy by transferrin provides a new perspective on the function modulation of nanomedicine via LMW PEGs.
纳米材料表面形成的蛋白质冠层（PC）的发现推动了对PC调控的研究，以指导纳米材料在体内的生物学行为。与改变纳米颗粒的大小、形状和表面电荷不同，我们建议通过调节颗粒表面低分子量聚乙二醇（LMW PEG，分子量不超过1000 Da）的分子量来控制PC的性质。在排除聚乙二醇化金纳米颗粒（GNP）物理化学因素的影响后，将聚乙二醇化GNP与人血浆孵育，分离并鉴定其表面的不同蛋白质。值得注意的是，带有550 Da PEG链的GNP-550比其他两种颗粒（即GNP-350和GNP-1000）吸收了更多负责肿瘤靶向的转铁蛋白。为了验证我们的推测，将阿霉素（Dox）插入GNP和PEG之间，以探索Dox偶联GNP的细胞和动物研究。有趣的是，含Dox的Conj-550对HepG2细胞也表现出最高的细胞内摄取、细胞毒性和凋亡，以及在荷肝癌小鼠中最佳的肿瘤靶向效果和抗肿瘤疗效。这种由转铁蛋白介导的蛋白质冠层引导的肿瘤靶向治疗为通过LMW PEGs调节纳米药物功能提供了新的视角。
