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

Abstract

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