Red Blood Cell-Mimic Nanocatalyst Triggering Radical Storm to Augment Cancer Immunotherapy

Red blood cells(RBCs)have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells,but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue.Herein,artificial RBCs(designated FTP@RBCM)with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal-organic frameworks(FTPs,as the core),including photodynamic/chemodynamic-like,catalase-like and glutathione peroxidase-like activities.Meanwhile,owing to the advantages of long circulation abilities of RBCs provided by their cell membranes(RBCMs),FTP with a surface coated with RBCMs(FTP@RBCM)could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency.Intriguingly,this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death,which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3(Tim-3)checkpoint blockade,leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors.Therefore,such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.

In situ sustained release hydrogel system delivering GLUT1 inhibitor and chemo-drug for cancer post-surgical treatment

Systematic administration of small molecular drugs often suffered from the low efficacy and systemic toxicity in cancer therapy.In addition,application of single mode drug usually leads to unsatisfactory therapeutic out-comes.Currently,developing multimodal-drug combination strategy that acts on different pathways without increasing side effects remains great challenge.Here,we developed a hydrogel system that co-delivered glycolysis inhibitor apigenin and chemo-drug gemcitabine to realize combination strategy for combating can-cer with minimal systemic toxicity.We demonstrated that this system can not only eliminate tumor cells in situ,but also induce abscopal effect on various tumor models.These results showed that our study provided a safe and effective strategy for clinical cancer treatment.