Deep penetration of nanoparticulate drug delivery systems into tumors: challenges and solutions.

In recent decades, nanoparticulate drug delivery systems have attracted extensive attention in cancer therapy for such appealing properties as small particle size, huge surface area, narrow size distribution and prolonged circulation time. Although several nanomedicines have successfully reached the clinical, evidences have proved that therapeutic efficacy isn't improved significantly, except for better toleration and less side effects. Given that the physiological abnormalities in tumors, multiple biobarriers need to be overcome before nanomedicines are delivered to the target site. Passive targeting nanoparticles ensure nanomedicines' extensive extravasation from tumor vessels via enhanced permeation and retention effect, but the diffusion distance is limited to 2-3 cell layer thicknesses. Active targeting nanoparticles tend to bind the peripheral cells of the tumor mass, hindering nanoparticles further penetration into the tumor core region. Therefore, how to improve the deep penetration of nanomedicines into tumors is a formidable task for achieving the desired anticancer therapeutic efficacy. This review demonstrates the penetration obstacles existing in tumor region for nanoparticles, summarizes the important properties of nanomedicines affecting tumor deep penetration and highlights the solutions to improve tumor deep penetration of nanoparticles.