Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
Nat Chem Biol. 2022 Sep;18(9):1023-1031. doi: 10.1038/s41589-022-01093-5. Epub 2022 Aug 11.
Nanotechnology provides platforms to deliver medical agents to specific cells. However, the nanoparticle's surface becomes covered with serum proteins in the blood after administration despite engineering efforts to protect it with targeting or blocking molecules. Here, we developed a strategy to identify the main interactions between nanoparticle-adsorbed proteins and a cell by integrating mass spectrometry with pooled genome screens and Search Tool for the Retrieval of Interacting Genes analysis. We found that the low-density lipoprotein (LDL) receptor was responsible for approximately 75% of serum-coated gold nanoparticle uptake in U-87 MG cells. Apolipoprotein B and complement C8 proteins on the nanoparticle mediated uptake through the LDL receptor. In vivo, nanoparticle accumulation correlated with LDL receptor expression in the organs of mice. A detailed understanding of how adsorbed serum proteins bind to cell receptors will lay the groundwork for controlling the delivery of nanoparticles at the molecular level to diseased tissues for therapeutic and diagnostic applications.
纳米技术为将医学制剂递送至特定细胞提供了平台。然而，尽管在工程设计方面采取了靶向或阻断分子等措施来保护纳米粒子，但在给药后，纳米粒子的表面仍会被血液中的血清蛋白所覆盖。在这里，我们开发了一种策略，通过将质谱与基因组筛选库和相互作用基因检索工具（Search Tool for the Retrieval of Interacting Genes analysis）整合，来鉴定吸附在纳米粒子上的蛋白质与细胞之间的主要相互作用。我们发现，低密度脂蛋白（LDL）受体大约负责 75%的 U-87 MG 细胞对金纳米粒子的摄取。纳米粒子上的载脂蛋白 B 和补体 C8 蛋白通过 LDL 受体介导摄取。在体内，纳米粒子的积累与小鼠器官中 LDL 受体的表达相关。深入了解吸附的血清蛋白如何与细胞受体结合，将为在分子水平上控制纳米粒子在疾病组织中的递释奠定基础，从而实现治疗和诊断应用。
