Strategies of overcoming the physiological barriers for tumor-targeted nano-sized drug delivery systems

Nano drug delivery systems (NDDSs) have been widely used in tumor-targeted therapy since they can effectively reduce the side effects of traditional antitumor drugs and improve the anti-tumor effect. We divided the in vivo process of tumor-targeted NDDSs into seven steps: blood circulation, tumor accumulation, tumor tissue penetration, target cells internalization, lysosome escape, drug release and drug response. In each step, NDDSs will encounter different types of barriers preventing their effective delivery or response. The researchers have been making efforts to find different strategies of overcoming the corresponding barriers for NDDSs. Hence, we here reviewed the recent progress of NDDSs in breaking the physiological barriers for more effective in vivo anti-tumor effect, in order to shed a new perspective on the development of tumor-targeted NDDSs.