ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, 250100, China.
Adv Healthc Mater. 2019 May;8(9):e1801607. doi: 10.1002/adhm.201801607. Epub 2019 Mar 14.
Low-fouling or "stealth" particles composed of poly(ethylene glycol) (PEG) display a striking ability to evade phagocytic cell uptake. However, functionalizing them for specific targeting is challenging. To address this challenge, stealth PEG particles prepared by a mesoporous silica templating method are functionalized with bispecific antibodies (BsAbs) to obtain PEG-BsAb particles via a one-step binding strategy for cell and tumor targeting. The dual specificity of the BsAbs-one arm binds to the PEG particles while the other targets a cell antigen (epidermal growth factor receptor, EGFR)-is exploited to modulate the number of targeting ligands per particle. Increasing the BsAb incubation concentration increases the amount of BsAb tethered to the PEG particles and enhances targeting and internalization into breast cancer cells overexpressing EGFR. The degree of BsAb functionalization does not significantly reduce the stealth properties of the PEG particles ex vivo, as assessed by their interactions with primary human blood granulocytes and monocytes. Although increasing the BsAb amount on PEG particles does not lead to the expected improvement in tumor accumulation in vivo, BsAb functionalization facilitates tumor cell uptake of PEG particles. This work highlights strategies to balance evading nonspecific clearance pathways, while improving tumor targeting and accumulation.
由聚乙二醇（PEG）组成的低污或“隐形”颗粒表现出惊人的逃避吞噬细胞摄取的能力。然而，对其进行特定靶向功能化具有挑战性。为了解决这一挑战，通过介孔硅模板法制备的隐形 PEG 颗粒用双特异性抗体（BsAb）进行功能化，通过一步结合策略获得用于细胞和肿瘤靶向的 PEG-BsAb 颗粒。BsAb 的双重特异性——一个臂与 PEG 颗粒结合，另一个臂靶向细胞抗原（表皮生长因子受体，EGFR）——被利用来调节每个颗粒上的靶向配体数量。增加 BsAb 孵育浓度会增加与 PEG 颗粒结合的 BsAb 数量，并增强对过表达 EGFR 的乳腺癌细胞的靶向和内化。从与原代人血液粒细胞和单核细胞的相互作用评估，BsAb 功能化不会显著降低 PEG 颗粒在体外的隐形特性。虽然增加 PEG 颗粒上的 BsAb 量不会导致体内肿瘤积累的预期改善，但 BsAb 功能化促进了肿瘤细胞对 PEG 颗粒的摄取。这项工作强调了平衡逃避非特异性清除途径的策略，同时提高肿瘤靶向和积累的策略。
