| Tumor-associated antigens(TAAs)-loaded nanoparticles are able to be actively internalized by antigen-presenting cells(APCs)and have shown promising potential in cancer immunotherapy.However,current TAAs delivery strategy exhibits limitations of complicated synthesis process,low loading efficiency and inefficient CD8+ cytotoxic Tlymphocyte activation leading to unsatisfactory therapeutic effect.Thus,the construction of novel TAAs-delivery systems for enhanced cancer therapy is highly desirable.In this work,pH-responsive metal-organic frameworks(MOFs)is fabricated by a very simple yet powerful antigens-delivery system for cancer immunotherapy.TAAs can be loaded into MOFs in the one-pot synthesis process and released with the degradation of MOFs in the acidic environment of endo/lysosome as the result of relatively labile metal-ligand bonds.The endosomolytic nanoparticles would facilitate protein antigens escape from endo/lysosome and optimal for enhancing antigen cross-presentation.Furthermore,the introduction of immunostimulatory unmethylated cytosine-phosphate-guanine oligonucleotide(CpG)through Watson-Crick base pairing would further enhance CD8+ cytotoxic T lymphocyte responses.We demonstrated that the method to co-delivery antigens and immunostimulatory molecules was very simple,convenient and effective and showed no obvious toxicity both in vitro and in vivo.This method gave a high antigens-loading capacity and the maximal antigen encapsulating efficiency was about 55%(w/w).Additionally,the pH-responsive co-delivery system exerted enhanced antitumor outcome(about 100% survival)in B16-OVA melanoma cancers in vivo.Furthermore,we confirmed that this high rating of therapeutic effect was attributed to the recruitment of tumor-killing immunocyte.This work demonstrates the ability of pH-responsive,endosomolytic MOFs to induce strong cellular immune responses for cancer therapy by co-delivery of CpG ODN and antigens. |
PDF Full Text Request