Reprogramming tumor microenvironment via systemic delivery of TLR3 agonist and manganese nanoparticle

Despite the promise of Toll-like receptor agonists as immune adjuvants, their antitumor efficacy has been limited in the clinic. Here, we report the development of a lipid nanoparticle system (PLCMP) designed for codelivery of a TLR3 agonist and Mn²⁺ and simultaneous activation of TLR3 and stimulator of interferon genes (STING) pathways. Systemic administration of PLCMP in combination with α-PD-1 therapy led to strong antitumor effects in multiple murine tumor models. In addition, we have demonstrated the potential of the PLCMP platform to deliver tumor antigens and induce antigen-specific T cell responses, leading to improved cancer vaccination.