ROS-Inducing Micelles Sensitize Tumor-Associated Dendritic cells to TLR3 Stimulation for Potent Immunotherapy

Objective To prepare ZnPP-PM nanoparticles based on peptide micelles (PM) loaded with zinc protoporphyrin IX (ZnPP) for targeted delivery of immune adjuvants, and to study their activation ability and anti-tumor effect on tumor associated dendritic cells (TADCs) derived from mouse bone marrow.Method ZnPP was connected to mannose functionalized PM block copolymers via amide bonds, self-assembled into ZnPP-PM with the ability to target DC and induce ROS, and loaded with PIC via electrostatic adsorption to form ZnPP-PM/PIC nanoparticles, which were characterized. Application of laser confocal microscopy and flow cytometry to detect the uptake ability of cells towards ZnPP-PM, as well as the effect of ZnPP-PM/PIC on the production and activation of reactive oxygen species (ROS) in TADCs. And verify the in vivo anti-tumor effect of ZnPP-PM/PIC through animal experiments.Result The particle sizes of ZnPP-PM and ZnPP-PM/PIC are approximately 33 ± 3.55 nm and 30 ± 2.47 nm, respectively, with no significant difference between the two. They have good dispersibility and stability, and exhibit specific targeting ability towards DC. In addition, ZnPP-PM/PIC can more effectively promote TADC activation by enhancing ROS production and PIC coordination (P<0.05), and induce more effective anti-tumor effects in vivo by increasing the activation of effector cells (CD8+CD69+, CD4+CD69+ or NK1.1+CD69+) in tumors and TDLNs.Conclusion Based on ZnPP-PM as a targeted transport immune adjuvant, promoting TADC activation can become a potential anti-tumor treatment strategy.