Biomimetic Nanoimmunotherapy Boostsspatiotemporal Panoptosis And Reshapesdesmoplastic Tumor Microenvironment Hui Huang by Hui Huang, Zebin Xiao, Wei Feng, Xinran Song, Liang Chen, Lili Huang, Li Ding, Yu Chen 10.1016/J.XCRM.2025.102312 instant download after payment.

SUMMARYDendritic cell (DC)-based vaccines for solid tumors face major challenges, including limited tumor-specificantigens and immunosuppressive stroma. Here, we present a therapeutic nanovaccine (UCNP@MOF@MI@FM [UMMF]) composed of a DC/tumor fused cytomembrane-coated UCNP@MOF nanoparticle, co-loadedwith a MutT homolog 1 (MTH1) inhibitor and combined with tetrahydrobiopterin (BH4). 

The fused membranefacilitates dual targeting to tumors and lymph nodes while enabling broad-spectrum tumor antigen presentation. Upon near-infrared (NIR) irradiation, upconversion-triggered reactive oxygen species (ROS) generation and MTH1 inhibition synergistically induce immunogenic PANoptosis, releasing antigens and promotingDCs maturation. Simultaneously, ROS remodels the tumor stroma by depleting collagen and cancer-associated fibroblasts, enhancing T cell infiltration. BH4 counteracts IDO-mediated kynurenine accumulation,reversing immune tolerance and restoring T cell function. This multifunctional platform integrates tumorcell killing, immune priming, and stromal reprogramming, resulting in robust antitumor immunity, reducedrelapse, and metastasis suppression. UMMF offers a promising strategy for precision nanoimmunotherapythrough controlled PANoptosis and microenvironment modulation.