Recent advances in drug delivery systems for enhancing drug penetration into tumors

The emergence of nanomaterials for drug delivery provides the opportunity to avoid the side effects of systemic drug administration and injury caused by the removal of tumors, delivering great promise for future cancer treatments. However, the efficacy of current nano drugs is not significantly better than that of the original drug treatments. The important reason is that nano drugs enter the tumor vasculature, remaining close to the blood vessels and unable to enter the tumor tissue or tumor cells to complete the drug delivery process. The low efficiency of drug penetration into tumors has become a bottleneck restricting the development of nano-drugs. Herein, we present a systematic overview of recent advances on the design of nano-drug carriers in drug delivery systems for enhancing drug penetration into tumors. The review is organized into four sections: The drug penetration process in tumor tissue includes paracellular and transcellular transport, which is summarized first. Strategies that promote tumor penetration are then introduced, including methods of remodeling the tumor microenvironment, charge inversion, dimensional change, and surface modification of ligands which promote tissue penetration. Conclusion and the prospects for the future development of drug penetration are finally briefly illustrated. The review is intended to provide thoughts for effective treatment of cancer by summarizing strategies for promoting the endocytosis of nano drugs into tumor cells.