Current understanding of passive and active targeting nanomedicines to enhance tumor accumulation

In recent years, tremendous advancements in nanomedicine have resulted in the rapid development of various nanoformulations, especially the treatment of solid tumors. Despite the enormous progress and success on the laboratory scale, the process of entering clinical application has been prolonged, as many have not achieved the desired therapeutic effect. The principal reason for their failure is that the accumulation of nanomedicine in tumors is often insufficient. In this review, we summarize the physicochemical properties of nanoparticles, tumor microenvironment regulation, active targeting, cell biomimetic, and transcytosis strategies to enhance tumor accumulation. Accordingly, the process and mechanism of nanomedicine in tumor accumulation are discussed, highlighting the mechanism of active targeting in enhancing the accumulation of nanoparticles. We speculated that the active targeting nanoparticles promote the internalization of tumor cells, which may be to reform the congestion of nanoparticles in tumor tissues and promote the continuous exudation of nanoparticles from blood vessels, increasing tumor accumulation. Further, these explicit discussions will help explore the process of tumor-targeted delivery systems and promote the clinical transformation of nanomedicines.