Harnessing cells to improve transport of nanomedicines

Efficient tumour treatment is hampered by the poor selectivity of anticancer drugs, resulting in scarce tumour accumulation and undesired off-target effects. Nano-sized drug-delivery systems in the form of nanoparticles (NPs) have been proposed to improve drug distribution to solid tumours, by virtue of their ability of passive and active tumour targeting. Despite these advantages, literature studies indicated that less than 1% of the administered NPs can successfully reach the tumour mass, highlighting the necessity for more efficient drug transporters in cancer treatment. Living cells, such as blood cells, circulating immune cells, platelets, and stem cells, are often found as an infiltrating component in most solid tumours, because of their ability to naturally circumvent immune recognition, bypass biological barriers, and reach inaccessible tissues through innate tropism and active motility. Therefore, the tumour-homing ability of these cells can be harnessed to design living cell carriers able to improve the transport of drugs and NPs to tumours. Albeit promising, this approach is still in its beginnings and suffers from difficult scalability, high cost, and poor reproducibility. In this review, we present an overview of the most common cell transporters of drugs and NPs, and we discuss how different cell types interact with biological barriers to deliver cargoes of various natures to tumours. Finally, we analyse the different techniques used to load drugs or NPs in living cells and discuss their advantages and disadvantages.