Matrix Metalloproteinase Cleavable Nanoparticles for Tumor Microenvironment and Tumor Cell Dual-Targeting Drug Delivery

Matrix metalloproteinases (MMPs), mostly abundant in the tumor extracellular matrix (ECM), tumor cells, and tumor vasculatures, are closely correlated with tumor progression and metastasis. In this case, making use of MMPs was supposed to achieve site-specific drug delivery and a satisfactory tumor treatment effect. Herein, we rationally developed a novel tumor microenvironment and tumor cell dual-targeting nanoparticle by integrating a chemotherapeutic-loaded drug-loaded carrier and a versatile polypeptide-LinTT1-PVGLIG-TAT (LPT) which is composed of a multitargeting peptide-LinTT1 and a cell-penetrating peptide-TAT. The functionalized nanoparticles exhibited a superior affinity to A549 lung-cancer cells and microenvironment including angiogenesis and tumor-associated macrophages (TAMs) in our study. In addition, cellular experiments demonstrated that the cell-penetrating ability of TAT was significantly shielded by the addition of LinTT1 to the fourth lysine of the TAT via an MMP cleavable linker PVGLIG...