Optimized Fabrication of Dendritic Mesoporous Silica Nanoparticles as Efficient Delivery System for Cancer Immunotherapy

In the past decade, cancer immunotherapy has revolutionized the field of oncology. Major immunotherapy approaches such as immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, cytokines, and immunomodulators have shown great promise in preclinical and clinical settings. Among them, immunomodulatory agents including cancer vaccines are particularly appealing; however, they face limitations, notably the absence of efficient and precise targeted delivery of immune-modulatory agents to specific immune cells and the potential for off-target toxicity. Nanomaterials can play a pivotal role in addressing targeting and other challenges in cancer immunotherapy. Dendritic mesoporous silica nanoparticles (DMSNs) can enhance the efficacy of cancer vaccines by enhancing the effective loading of immune modulatory agents owing to their tunable pore sizes. In this work, an emulsion-based method is optimized to customize the pore size of DMSNs and loaded DMSNs with ovalbumin (OVA) and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (CpG-OVA-DMSNs). The immunotherapeutic effect of DMSNs is achieved through controlled chemical release of OVA and CpG in antigen-presenting cells (APCs). The results demonstrated that CpG-OVA-DMSNs efficiently activated the immune response in APCs and reduced tumor growth in the murine B16-OVA tumor model.