Research progress of tumor targeted drug delivery based on PD-1/PD-L1.

Over activation of immune checkpoint pathways assists tumor cells to escape the surveillance of immune system, resulting in generation and development of tumor. Drugs blocking immune checkpoints target lymphocyte receptors or their ligands to enhance endogenous antitumor activity by activating the immune system. The drugs targeting PD-1/PD-L1 axis have achieved favourable clinical efficacy, less and controllable toxicity and side effects. However, only a part of patients benefit from immunotherapy, so the problem of increasing the response rate of patients is on the agenda. Meanwhile, there are still some problems such as how to achieve the long-term response to most metastatic or non operative malignant tumors, and minimize the side effects of immune checkpoint inhibitor (ICI). Therefore, scientists are actively exploring methods, such as combining anti-PD-1 therapy with various traditional or newly developed therapeutic methods and building a tumor targeted drug delivery system to maximize the efficacy of drugs and reduce side effects. In this review, we summarized the related concepts and mechanism of PD-1 and its ligands PD-L1, and introduced certain drugs targeting PD-1/PD-L1 axis, their clinical effects and safety issues. Finally, a variety of combination therapies based on PD-1/PD-L1 and the application of different nanocarriers aiming at reducing non-targeting effect and improving the efficacy were discussed.