Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
Research Centre for Regenerative Medicine, Department of Orthopedics, The First Affiliated Hospital of Gaungxi Medical University, Nanning, 530021, China.
J Nanobiotechnology. 2020 Aug 27;18(1):117. doi: 10.1186/s12951-020-00666-7.
Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA), which enables the development of stimulus-responsive drug delivery system with high specificity for OA. We herein demonstrate a nano-micelle based stimuli-responsive theranostic strategy with reporting and drug release controlled by acidic pH and MMP-13 for OA therapy. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an anti-inflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro and vivo evidences.
刺激响应性治疗仅在感兴趣的病变部位精确控制治疗效果，这使其成为诊断和成像引导的精准治疗的有前途的方法。酸性环境和过表达的基质金属蛋白酶-13（MMP-13）是骨关节炎（OA）的典型标志物，这使得具有针对 OA 高度特异性的刺激响应性药物递送系统的发展成为可能。我们在此展示了一种基于纳米胶束的刺激响应性治疗策略，该策略通过酸性 pH 和 MMP-13 控制报告和药物释放，用于 OA 治疗。该纳米平台结合了一种专门针对软骨的基序、一种响应基质金属蛋白酶-13 的基序，以专门报告 OA 状况和纳米胶束的生物动力学，一种来自中药的抗炎药物（如补骨脂素（PSO）），以及一种生物相容性聚合物骨架，以响应酸性 OA 条件持续释放药物。通过体外和体内证据全面证明了这种靶向精准治疗的高效性。
