pH-Responsive Metal–Organic Framework-Coated\nMesoporous Silica Nanoparticles for Immunotherapy

Abstract

Various\nnanovesicles loaded with tumor-associated antigens (TAAs)\nhave been developed for melanoma treatment. However, the slow release\nof antigens leads to an ineffective immune response. pH-responsive\ngatekeepers have been reported for achieving “zero release”,\nbut the complicated synthesis process limits their applications. Therefore,\nit is essential to develop a simple and easy-to-synthesize gatekeeper\nfor the controlled release of proteins. In our work, mesoporous silica\nnanoparticles (MSNs) were used for model vaccine ovalbumin (OVA) loading.\nMetal–organic frameworks (MOFs) with pH-responsive ability\nwere synthesized as gatekeepers via a one-step method, coordinating\nEu ions with guanine monophosphate (GMP) on the MSN surface. CpG oligodeoxynucleotides\nwere used as TLR9 agonists, which could specifically bind to the MSN-OVA@MOF\nsurface through Watson–Crick base pairing for further promoting\nimmune responses. Our work has demonstrated that MOF-coated MSN could\nbe effectively co-loaded with OVA and CpG (MSN-OVA@MOF@CpG) and present\nantigens to antigen-presenting cells. The coated MOF, as gatekeepers,\ncan be degraded in endo/lysosomes and release OVA and CpG, which then\ninduces more vital OVA-specific T cell responses for high-efficient\ninhibition of melanoma cancer growth and metastasis.