Coordination Polymers Integrating Metalloimmunology with Immune Modulation to Elicit Robust Cancer Chemoimmunotherapy

Nanoscale coordination polymers (NCPs) constructed by metal ions and organic ligands via metal–ligand bonds have attracted great attention for their biomedical application. Herein, a new type of NCP is constructed from Zn-ions and 4-phenylimidazole (PI), the latter of which is an inhibitor of indoleamine 2,3-dioxygenase (IDO) and acts as an organic bridging ligand via Zn–N coordination bonds. After modification with polyethylene glycol (PEG) and further loading with an immunogenic cell death (ICD) inducing therapeutic, doxorubicin (DOX), the metal-ligand coordination complex, ZnPI-PEG/DOX NCPs obtained, could be utilized as an effective cancer chemoimmunotherapy. In this system, Zn-ions cell membrane surface exposure of calreticulin (CRT) to enhance DOX-triggered ICD of tumor cells, while PI reversed the immunosuppressive tumor microenvironment (TME) by inhibiting IDO. Such synergistic action effects dramatically elicited antitumor immune responses, leading to inhibition of tumor growth, along with facilitation of long-term immune memory effect. Our work presents a smart design of NCPs as a “carrier-free” drug delivery system that enabled highly effective chemoimmunotherapy in cancer treatment.