Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
Biomacromolecules. 2022 Jan 10;23(1):339-348. doi: 10.1021/acs.biomac.1c01295. Epub 2021 Dec 10.
Disulfide cross-linked nanoassemblies have attracted considerable attention as a drug delivery vehicle due to their responsiveness to the natural redox gradient in biology. Fundamentally understanding the factors that influence the drug loading capacity, encapsulation stability, and precise control of the liberation of encapsulated cargo would be profoundly beneficial to redox-responsive materials. Reported herein are block copolymer (BCP)-based self-cross-linked nanogels, which exhibit high drug loading capacity, high encapsulation stability, and controllable release kinetics. BCP nanogels show considerably higher loading capacity and better encapsulation stability than the random copolymer nanogels at micromolar glutathione concentrations. By partially substituting thiol-reactive pyridyl disulfide into the unreactive benzyl or butyl group, we observed opposite effects on the cross-linking process of BCP nanogels. We further studied the redox-responsive cytotoxicity of our drug-encapsulated nanogels in various cancer cell lines.
二硫键交联纳米组装体因其对生物学中天然氧化还原梯度的响应而引起了相当大的关注，作为一种药物输送载体。从根本上理解影响药物装载能力、封装稳定性以及封装货物精确释放的因素，将对氧化还原响应材料有深远的益处。本文报道了基于嵌段共聚物 (BCP) 的自交联纳米凝胶，其表现出高药物装载能力、高封装稳定性和可控的释放动力学。在微摩尔谷胱甘肽浓度下，BCP 纳米凝胶的载药能力和封装稳定性明显高于无规共聚物纳米凝胶。通过将部分巯基反应性吡啶二硫键部分取代为非反应性的苄基或丁基，我们观察到对 BCP 纳米凝胶的交联过程有相反的影响。我们进一步研究了我们包载药物的纳米凝胶在各种癌细胞系中的氧化还原响应性细胞毒性。
