Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.
Department of Chemistry, Bogazici University, Istanbul 34342, Turkey.
ACS Appl Mater Interfaces. 2023 Mar 29;15(12):15260-15268. doi: 10.1021/acsami.3c02640. Epub 2023 Mar 15.
Bioorthogonal activation of pro-dyes and prodrugs using transition-metal catalysts (TMCs) provides a promising strategy for imaging and therapeutic applications. TMCs can be loaded into polymeric nanoparticles through hydrophobic encapsulation to generate polymeric nanocatalysts with enhanced solubility and stability. However, biomedical use of these nanostructures faces challenges due to unwanted tissue accumulation of nonbiodegradable nanomaterials and cytotoxicity of heavy-metal catalysts. We report here the creation of fully biodegradable nanocatalysts based on an engineered FDA-approved polymer and the naturally existing catalyst hemin. Stable nanocatalysts were generated through kinetic stabilization using flash nanoprecipitation. The therapeutic potential of these nanocatalysts was demonstrated through effective treatment of bacterial biofilms through the bioorthogonal activation of a pro-antibiotic.
利用过渡金属催化剂(TMCs)对前体染料和前药进行生物正交激活,为成像和治疗应用提供了一种很有前途的策略。TMC 可以通过疏水包封装入聚合物纳米粒子中,以生成具有增强的溶解度和稳定性的聚合物纳米催化剂。然而,由于不可生物降解的纳米材料在组织中的不必要积累和重金属催化剂的细胞毒性,这些纳米结构的生物医学用途面临挑战。我们在这里报告了基于经 FDA 批准的工程聚合物和天然存在的催化剂血红素的完全可生物降解纳米催化剂的创建。通过使用快速纳米沉淀进行动力学稳定化,生成了稳定的纳米催化剂。通过生物正交激活前抗生素,有效治疗细菌生物膜,证明了这些纳米催化剂的治疗潜力。