Li Xuying, Xu Zhuping
Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China.
Pharmaceutics. 2025 Apr 7;17(4):479. doi: 10.3390/pharmaceutics17040479.
Matrix metalloproteinase-9 (MMP-9) is implicated in tumor progression and vascular diseases, contributing to angiogenesis, metastasis, and extracellular matrix degradation. This review comprehensively examines the relationship between MMP-9 and these pathologies, exploring the underlying molecular mechanisms and signaling pathways involved. Specifically, we discuss the contribution of MMP-9 to tumor epithelial-mesenchymal transition, angiogenesis, and metastasis, as well as its involvement in a spectrum of vascular diseases, including macrovascular, cerebrovascular, and ocular vascular diseases. This review focuses on recent advances in MMP-9-targeted nanomedicine strategies, highlighting the design and application of responsive nanoparticles for enhanced drug delivery. These nanotherapeutic strategies leverage MMP-9 overexpression to achieve targeted drug release, improved tumor penetration, and reduced systemic toxicity. We explore various nanoparticle platforms, such as liposomes and polymer nanoparticles, and discuss their mechanisms of action, including degradation, drug release, and targeting specificity. Finally, we address the challenges posed by the heterogeneity of MMP-9 expression and their implications for personalized therapies. Ultimately, this review underscores the diagnostic and therapeutic potential of MMP-9-targeted nanomedicines against tumors and vascular diseases.
基质金属蛋白酶-9（MMP-9）与肿瘤进展和血管疾病有关，在血管生成、转移和细胞外基质降解中发挥作用。本综述全面研究了MMP-9与这些病症之间的关系，探讨了潜在的分子机制和涉及的信号通路。具体而言，我们讨论了MMP-9对肿瘤上皮-间质转化、血管生成和转移的作用，以及它在一系列血管疾病中的参与情况，包括大血管疾病、脑血管疾病和眼部血管疾病。本综述重点关注MMP-9靶向纳米医学策略的最新进展，强调用于增强药物递送的响应性纳米颗粒的设计和应用。这些纳米治疗策略利用MMP-9的过表达来实现靶向药物释放、改善肿瘤渗透并降低全身毒性。我们探索了各种纳米颗粒平台，如脂质体和聚合物纳米颗粒，并讨论了它们的作用机制，包括降解、药物释放和靶向特异性。最后，我们阐述了MMP-9表达异质性带来的挑战及其对个性化治疗的影响。最终，本综述强调了MMP-9靶向纳米药物在对抗肿瘤和血管疾病方面的诊断和治疗潜力。
