LAUSR

In this study, an ingenious core-shell structure microneedles (CSMNs) array was designed to synergistically boost robust immune response by intralesional co-delivery of photosensitizer and indoleamine 2,3-dioxygenase (IDO) blockade. Photosensitizer indocyanine green was encapsulated into chitosan nanoparticles (ICG-NPs), followed by concentrating on the tip shell of microneedles. 1-methyl-tryptophan (1-MT) was loaded into the cross-linked poly (vinyl alcohol) and poly (vinyl pyrrolidone) gel as the microneedle core. Through directly depositing the ICG-NPs loaded tips into the tumor site with uniform spatial distribution, the CSMNs effectively converted the near-infrared laser into heat to ablate primary tumors, generated tumor-associated antigens and damage-associated molecular patterns (DAMPs), promoted dendritic cell maturation and immunostimulatory cytokines secretion. The IDO blockade further downregulated the IDO-mediated immunosuppression, ultimately aroused an effective systematic immune response. The in vivo results showed that 80% of melanoma tumor was eradicated, followed by a relapse-free survival in more than 120 days. Remarkably, this combination therapy significantly inhibited lung metastasis and controlled the growth of already metastasized tumors. Our work provide a new, generalizable framework for using microneedle-based photothermal therapy to initiate antitumor immunity and sensitize tumor to IDO blockade.