Standard small molecule and nanoparticulate
chemotherapies are used for
cancer treatment; however, their effectiveness remains highly variable. One reason for this variable response is hypothesized to be due to nonspecific drug distribution and heterogeneity of the tumor microenvironment, which affect
tumor delivery of the agents. Nanoparticle drugs have many theoretical advantages, but due to variability in tumor microenvironment (TME) factors, the overall drug delivery to
tumors and associated antitumor response are low. The nanotechnology field would greatly benefit from a thorough analysis of the TME factors that create these physiological barriers to
tumor delivery and treatment in preclinical models and in patients. Thus, there is a need to develop methods that can be used to reveal the content of the TME, determine how these TME factors affect drug delivery, and modulate TME factors to increase the
tumor delivery and efficacy of nanoparticles. In this review, we will discuss TME factors involved in drug delivery, and how biomedical imaging tools can be used to evaluate
tumor barriers and predict drug delivery to
tumors and antitumor response.