Nano-Drug Delivery Systems Targeting MMPs: A Promising Treatment for Gliomas.

Gliomas are the most prevalent Central Nervous System (CNS) tumors. Among them, glioblastoma (grade IV) is the most challenging brain cancer because of its highly aggressive nature, treatment resistance and poor prognosis. Matrix metalloproteinase (MMP) is a family of zinc-dependent protein hydrolases. In recent years, MMPs have become a research focus owing to their central role in tumor microenvironment remodeling, angiogenesis, invasion, metastasis. Clinical studies have shown that the expression levels of MMPs in glioma tissues exhibit a significant positive correlation with the degree of malignancy and aggressiveness of gliomas. Therefore, the idea of MMPs as a detection target and therapeutic target can be proposed. Nanoparticle drug delivery system, as a cutting-edge technology, has shown great potential and broad prospects in clinical applications. The system realizes the targeted delivery, sustained-release control and bioavailability of drugs, and provides new ideas and means for the management of various pathological conditions. In this review, we will comprehensively discuss the expression relationship and major regulatory mechanisms between MMPs and gliomas, the composition of nano-drug delivery systems, routes of administration, and common types of nanomaterials used for the treatment of gliomas. In addition, we focus on cell-penetrating peptides (CPPs) as an entry point. We summarize the common kinds of activatable CPPs and how they are applied in nano-drug delivery systems. It is also found that MMP-responsive systems, which can be used for the treatment of gliomas, can activate CPPs, and through the synergistic effect between CPPs and MMPs, MMPs can be used as detection or therapeutic targets and combined with nano-drug delivery system for the medical management of gliomas. The nano-drug delivery system can demonstrate exceptional blood-brain barrier (BBB) penetration efficiency and precisely target the glioma region to release the drug. This delivery approach may prove to be beneficial for glioma patients.