The First Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, China.
State Key Laboratory of Optoelectronic Materials and Technologies, School of Electronics and Information Technology, Sun Yat-Sen University, Guangzhou, China.
J Adv Res. 2023 Jun;48:61-74. doi: 10.1016/j.jare.2022.08.015. Epub 2022 Aug 28.
Reducing the protein adsorption of nanoparticles (NPs) as drug carriers to slow their rapid clearance by macrophages uptake is a critical challenge for NPs clinical translational applications. Despite extensive research efforts to inhibit cellular uptake, including covering biological agents or surface chemical coatings to impart "stealth" properties to NPs, their stability remains insufficient.
Developed a novel surface modification technology based on a physical infusion engineering approach to achieve persistent inhibition of protein adhesion and cellular uptake by nanocarriers.
The nanoparticles were prepared based on conventional drug carrier mesoporous silica NPs through a two-step process. A functional nanoscale slippery surface was formed by grafting "liquid-like" brushes on the particles surface, and then a lubricant-entrenched slippery surfaces (LESS) was formed by infusing silicone oil lubricant into the entire surface. Co-incubation with macrophages (in vitro and in vivo) was used to examine the anti-uptake properties of modified NPs. The anti-adhesion properties of LESS coating surfaces to various liquids, proteins and cells were used to analyze the anti-uptake mechanism. Loaded with drugs, combined with tumor models, to evaluate the drug utilization of modified NPs.
Relying on the stable and slippery LESS coating, the modified surface could prevent the adhesion of various liquids and effectively shield against the adhesion of proteins and cells, as well as remarkably reduce macrophage cellular uptake in vitro and in vivo. In addition, the LESS coating does not affect cell activity and allows NPs to be loaded with drugs, significantly improving the utilization of drugs in vitro and in vivo. This allows the NPs to reach to the target tumor site for drug delivery without active clearance by macrophages.
Our research introduces a new nanocarrier technology to improve anti-biofouling performance and stealth efficiency that will facilitate the development of nanomedicines for clinical transformation applications.
减少纳米粒子（NPs）作为药物载体的蛋白质吸附，以减缓其被巨噬细胞摄取的快速清除，是 NPs 临床转化应用的一个关键挑战。尽管已经进行了广泛的研究来抑制细胞摄取，包括覆盖生物制剂或表面化学涂层来赋予 NPs“隐身”特性，但它们的稳定性仍然不足。
开发了一种基于物理注入工程方法的新型表面修饰技术，以实现纳米载体对蛋白质黏附和细胞摄取的持久抑制。
通过两步法，基于常规药物载体介孔硅 NPs 制备纳米颗粒。通过在颗粒表面接枝“液态”刷，在颗粒表面形成功能纳米级滑润表面，然后将硅油润滑剂注入整个表面，形成含润滑剂的滑润表面（LESS）。通过与巨噬细胞（体外和体内）共孵育，来考察修饰 NPs 的抗摄取性质。通过分析 LESS 涂层表面对各种液体、蛋白质和细胞的抗黏附性质，来研究抗摄取机制。负载药物后，结合肿瘤模型，评估修饰 NPs 的药物利用情况。
依赖于稳定且滑润的 LESS 涂层，修饰后的表面可以防止各种液体的黏附，并有效地防止蛋白质和细胞的黏附，显著减少体外和体内巨噬细胞的摄取。此外，LESS 涂层不影响细胞活性，并且允许 NPs 负载药物，显著提高了体外和体内药物的利用。这使得 NPs 能够到达靶肿瘤部位进行药物输送，而不会被巨噬细胞主动清除。
我们的研究介绍了一种新的纳米载体技术，以提高抗生物污染性能和隐身效率，这将有助于纳米医学向临床转化应用的发展。
