No abstract

Immunotherapy techniques, such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T cell therapies and cancer vaccines, have been burgeoning with great success, particularly for specific cancer types. However, side effects with fatal risks, dysfunction in tumor microenvironment and low immune response rates remain the bottlenecks in immunotherapy. Nano metal-organic frameworks (nMOFs), with an accurate structure and a narrow size distribution, are emerging as a solution to these problems. In addition to their function of temporospatial delivery, a large library of their compositions, together with flexibility in chemical interaction and inherent immune efficacy, offers opportunities for various designs of nMOFs for immunotherapy. In this review, we overview state-of-the-art research on nMOFs-based immunotherapies as well as their combination with other therapies. We demonstrate that nMOFs are predominantly customized for vaccine delivery or tumor-microenvironment modulation. Finally, a prospect of nMOFs in cancer immunotherapy will be discussed.

Lactate plays a critical role in tumorigenesis, invasion and metastasis. Exhausting lactate in tumors holds great promise for the reversal of the immunosuppressive tumor microenvironment (TME). Herein, we report on a “lactate treatment plant” (i.e., nanofactory) that can dynamically trap pro-tumor lactate and in situ transformation into anti-tumor cytotoxic reactive oxygen species (ROS) for a synergistic chemodynamic and metabolic therapy. To this end, lactate oxidase (LOX) was nano-packaged by cationic polyethyleneimine (PEI), assisted by a necessary amount of copper ions (PLNPCu). As a reservoir of LOX, the tailored system can actively trap lactate through the cationic PEI component to promote lactate degradation by two-fold efficiency. More importantly, the byproducts of lactate degradation, hydrogen peroxide (H2O2), can be transformed into anti-tumor ROS catalyzing by copper ions, mediating an immunogenic cell death (ICD). With the remission of immunosuppressive TME, ICD process effectively initiated the positive immune response in 4T1 tumor model (88% tumor inhibition). This work provides a novel strategy that rationally integrates metabolic therapy and chemodynamic therapy (CDT) for combating tumors. Graphical Abstract