Intracellular Delivery of Functional Native Antibodies under Hypoxic Conditions by Using a Biodegradable Silica Nanoquencher. (7th September 2017)

• Record Type: Journal Article
• Authors: Yuan, Peiyan; Zhang, Hailong; Qian, Linghui; Mao, Xin; Du, Shubo; Yu, Changmin; Peng, Bo; Yao, Shao Q.
• Is Part Of: Angewandte Chemie. Volume 129:Number 41(2017)
• Page Start: 12655
• Page End: 12659
• Publication Date: 2017-09-07
• Subjects: Antikörper -- Biologische Bildgebung -- Hypoxie -- Nanopartikel -- Wirkstofftransport; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201705578
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Antibodies are important biopharmaceuticals, but almost all existing antibody‐based drugs are limited to targeting antigens located at the cell exterior because of the inability of antibodies to enter the cell interior. Available methods for intracellular delivery of antibodies have major shortcomings. Herein, we report an approach to encapsulate native antibodies in a biodegradable silica nanoquencher (BS‐qNP), which could undergo efficient cellular uptake and intracellular degradation to release antibodies only under hypoxic conditions. By coating the surface of BS‐qNP with cell‐penetrating poly(disulfide)s (CPD), the delivered antibodies (or other proteins) avoided endolysosomal trapping. Doping of the silica coating with a fluorescent dye and a dark hole quencher further endowed BS‐qNP with hypoxia‐responsive fluorescence turn‐on property. Our antibody delivery system thus provides the first platform capable of stable encapsulation, efficient uptake, on‐demand antibody release, and imaging of release/cell state. Abstract : Überwachter Transport : Ein hypoxieresponsiver antikörperverkapselter Silica‐Nanolöscher wurde entwickelt und für die endocytoseunabhängige Aufnahme von nativen therapeutischen Antikörpern in Krebszellen und ihre gezielte Freisetzung dort genutzt. Die Antikörperfreisetzung und der hypoxische Zustand der Zelle lassen sich simultan abbilden.