Breaking the niche: multidimensional nanotherapeutics for tumor microenvironment modulation

Abstract

Most of the current antitumor therapeutics were developed targeting the cancer cells only. Unfortunately, in the majority of tumors, this single-dimensional therapy is found to be inefective. Advanced research has shown that cancer is a multicellular disorder. The tumor microenvironment (TME), which is made by a complex network of the bulk tumor cells and other sup porting cells, plays a crucial role in tumor progression. Understanding the importance of the TME in tumor growth, diferent treatment modalities have been developed targeting these supporting cells. Recent clinical results suggest that simultane ously targeting multiple components of the tumor ecosystem with drug combinations can be highly efective. This type of “multidimensional” therapy has a high potential for cancer treatment. However, tumor-specifc delivery of such multi-drug combinations remains a challenge. Nanomedicine could be utilized for the tumor-targeted delivery of such multidimensional therapeutics. In this review, we frst give a brief overview of the major components of TME. We then highlight the latest developments in nanoparticle-based combination therapies, where one drug targets cancer cells and other drug targets tumor supporting components in the TME for a synergistic efect. We include the latest preclinical and clinical studies and discuss innovative nanoparticle-mediated targeting strategies.