Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering , Shandong University , Jinan , Shandong 250100 , China.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering , The University of Melbourne , Parkville , Victoria 3010 , Australia.
Biomacromolecules. 2019 Sep 9;20(9):3592-3600. doi: 10.1021/acs.biomac.9b00925. Epub 2019 Aug 26.
Drug carriers typically require both stealth and targeting properties to minimize nonspecific interactions with healthy cells and increase specific interaction with diseased cells. Herein, the assembly of targeted poly(ethylene glycol) (PEG) particles functionalized with cyclic peptides containing Arg-Gly-Asp (RGD) (ligand) using a mesoporous silica templating method is reported. The influence of PEG molecular weight, ligand-to-PEG molecule ratio, and particle size on cancer cell targeting to balance stealth and targeting of the engineered PEG particles is investigated. RGD-functionalized PEG particles (PEG-RGD particles) efficiently target U-87 MG cancer cells under static and flow conditions in vitro, whereas PEG and cyclic peptides containing Arg-Asp-Gly (RDG)-functionalized PEG (PEG-RDG) particles display negligible interaction with the same cells. Increasing the ligand-to-PEG molecule ratio improves cell targeting. In addition, the targeted PEG-RGD particles improve cell uptake via receptor-mediated endocytosis, which is desirable for intracellular drug delivery. The PEG-RGD particles show improved tumor targeting (14% ID g) when compared with the PEG (3% ID g) and PEG-RDG (7% ID g) particles in vivo, although the PEG-RGD particles show comparatively higher spleen and liver accumulation. The targeted PEG particles represent a platform for developing particles aimed at balancing nonspecific and specific interactions in biological systems.
药物载体通常需要具有隐身和靶向特性，以最大限度地减少与健康细胞的非特异性相互作用，并增加与病变细胞的特异性相互作用。本文报道了通过介孔硅模板法组装靶向聚乙二醇（PEG）颗粒，这些颗粒用含有精氨酸-甘氨酸-天冬氨酸（RGD）的环肽（配体）进行功能化。研究了 PEG 分子量、配体与 PEG 分子的比例和颗粒大小对癌症细胞靶向性的影响，以平衡工程化 PEG 颗粒的隐身性和靶向性。PEG-RGD 颗粒在体外静态和流动条件下可有效靶向 U-87 MG 癌细胞，而含有精氨酸-天冬氨酸-甘氨酸（RDG）的 PEG（PEG-RDG）和环肽功能化的 PEG 颗粒与相同细胞几乎没有相互作用。增加配体与 PEG 分子的比例可提高细胞靶向性。此外，靶向 PEG-RGD 颗粒通过受体介导的内吞作用提高了细胞摄取率，这对于细胞内药物输送是理想的。与 PEG（3%ID g）和 PEG-RDG（7%ID g）颗粒相比，PEG-RGD 颗粒在体内显示出更好的肿瘤靶向性（14%ID g），尽管 PEG-RGD 颗粒的脾脏和肝脏积累相对较高。靶向 PEG 颗粒为开发旨在平衡生物系统中非特异性和特异性相互作用的颗粒提供了一个平台。
