Strategies to improve drug penetration into tumor microenvironment by nanoparticles: Focus on nanozymes

Solid tumors are composed of a complex organ-like structure, comprising tumor, immune and stromal cells, extracellular matrix (ECM), and blood vessels. Tumor microenvironments (TME), including ECM, make up the majority of the tumor and greatly influence the intratumor signaling, metabolism, and oxygen supply. As the ECM volume increases in the tumor, blood vessels do not penetrate the solid tumor, malignant cells in the hypoxic layer enter a dormant state, and the anticancer drug cannot penetrate the inner mass of the tumor to inhibit tumor activity. As a result, the effectiveness of radiotherapy, chemotherapy, and immunotherapy is reduced. Nanozyme is a type of nanomaterial with enzymatic properties that can play a role in reducing the ECM stiffness of tumor mass in a process which is called Nanocatalytic Tumor Therapy. This emerging technology is based on nontoxic inorganic nanoparticles (NPs) that kill the tumor by creating oxygen toxicity and reactive oxygen species (ROS) in the inner part of the tumor. Research into the therapeutic effect of these nanozymes is in its infancy and is growing, which could open a new window into overcoming tumor drug resistance.