Mn-coordination driven glutamine and cancer stemness dual-tailored nano-herb for high-efficiency activation of dendritic cells.

Abstract

Dendritic cells (DCs), as specialized antigen-presenting cells, are the commanders of the human immune cell system, directing and controlling various functions of the immune system. However, the competitive plunder of glutamine by tumor cells and the cancer cell stemness significantly impair the functional activation of DCs. Herein, we developed a Mn-coordination driven glutamine and cancer stemness dual-tailored nano-herb (HA/E-M@Purpurin NPs) for high-efficiency activation of DCs. The nano-herb is composed of ellagic acid (EA), divalent manganese ion (Mn²⁺), and purpurin. EA exerts an inhibitory effect on cell stemness, Mn²⁺ activate DCs by activating the cGAS-STING pathway, and purpurin inhibits the breakdown of glutamine, leading to a compensatory increase in glutamine content and further activating DCs. After surface modification with hyaluronic acid (HA), the nano-herb can target tumor cells and release drugs to exert corresponding effects. Taken together, our findings underscore the substantial promise of nano-herbs in overcoming cancer stemness-driven immune escape, offering a transformative approach to enhance the success of immunotherapy regimens.