1. Bioresponsive Polyphenol-Based Nanoparticles as Thrombolytic Drug Carriers
- Author
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Haitao Yu, Jason S. Palazzolo, Jiajing Zhou, Yingjie Hu, Be’eri Niego, Shuaijun Pan, Yi Ju, Ting-Yi Wang, Zhixing Lin, Christoph E. Hagemeyer, and Frank Caruso
- Subjects
Drug Carriers ,Temperature ,Polyphenols ,Biocompatible Materials ,Thrombosis ,Cell Line ,Mice ,Drug Delivery Systems ,Fibrinolytic Agents ,Tissue Plasminogen Activator ,Materials Testing ,Animals ,Humans ,Nanoparticles ,Thrombolytic Therapy ,General Materials Science - Abstract
Thrombolytic (clot-busting) therapies with plasminogen activators (PAs) are first-line treatments against acute thrombosis and ischemic stroke. However, limitations such as narrow therapeutic windows, low success rates, and bleeding complications hinder their clinical use. Drug-loaded polyphenol-based nanoparticles (NPs) could address these shortfalls by delivering a more targeted and safer thrombolysis, coupled with advantages such as improved biocompatibility and higher stability in vivo. Herein, a template-mediated polyphenol-based supramolecular assembly strategy is used to prepare nanocarriers of thrombolytic drugs. A thrombin-dependent drug release mechanism is integrated using tannic acid (TA) to cross-link urokinase-type PA (uPA) and a thrombin-cleavable peptide on a sacrificial mesoporous silica template via noncovalent interactions. Following drug loading and template removal, the resulting NPs retain active uPA and demonstrate enhanced plasminogen activation in the presence of thrombin (1.14-fold
- Published
- 2022