ABSTRACT
Vaccines harness the inherent properties of the immune system to prevent diseases or treat existing ones. Continuous efforts have been devoted to both gaining a mechanistic understanding of how the immune system operates and designing vaccines with high efficacies and effectiveness. Advancements in nanotechnology in recent years have generated unique opportunities to meet the daunting challenges associated with immunology and vaccine development. Firstly, nanoparticle formulated systems provide ideal model systems for studying the operation of the immune system, making it possible to systematically identify key factors and understand their roles in specific immune responses. Also, the versatile compositions/architectures of nanoparticle systems enable new strategies/novel platforms for developing vaccines with high efficacies and effectiveness. In this review, we discuss the advantages of nanoparticles and the challenges faced during vaccine development, through the framework of the immunological mechanisms of vaccination, with the aim of bridging the gap between immunology and materials science, which are both involved in vaccine design. The knowledge obtained provides general guidelines for future vaccine development.
Subject(s)
Nanoparticles/chemistry , Vaccines , Animals , Humans , Vaccination , Vaccines/chemistry , Vaccines/immunologyABSTRACT
For efficient cancer vaccines, the antitumor function largely relies on cytotoxic T cells, whose activation can be effectively induced via antigen-encoding mRNA, making mRNA-based cancer vaccines an attractive approach for personalized cancer therapy. While the liposome-based delivery system enables the systemic delivery and transfection of mRNA, incorporating an adjuvant that is non-lipid like remains challenging, although the co-delivery of mRNA (antigen) and effective adjuvant is key to the activation of the cytotoxic T cells. This is because the presence of an adjuvant is important for dendritic cell maturation-another necessity for cytotoxic T cell activation. In the present work, we designed a poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid nanoparticle carrier for the co-delivery of mRNA and gardiquimod (adjuvant that cannot be incorporated into the lipid shell). We demonstrated in the present work that the co-delivery of mRNA and gardiquimod led to the effective antigen expression and DC maturation in vitro. The intravenous administration of the hybrid nanovaccine resulted in the enrichment of mRNA expression in the spleen and a strong immune response in vivo. The simultaneous delivery of the antigen and adjuvant both spatially and temporally via the core/shell nanoparticle carrier is found to be beneficial for tumor growth inhibition.
Subject(s)
Adjuvants, Immunologic , Aminoquinolines , Cancer Vaccines , Imidazoles , Nanoparticles , Neoplasms, Experimental , RNA, Neoplasm , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacokinetics , Adjuvants, Immunologic/pharmacology , Aminoquinolines/chemistry , Aminoquinolines/pharmacokinetics , Aminoquinolines/pharmacology , Animals , Antigen Presentation/drug effects , Antigen Presentation/immunology , Cancer Vaccines/chemistry , Cancer Vaccines/pharmacokinetics , Cancer Vaccines/pharmacology , Cell Line, Tumor , Dendritic Cells/immunology , Dendritic Cells/pathology , Imidazoles/chemistry , Imidazoles/pharmacokinetics , Imidazoles/pharmacology , Liposomes , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neoplasms, Experimental/immunology , Neoplasms, Experimental/pathology , Neoplasms, Experimental/therapy , Polyglycolic Acid/chemistry , Polyglycolic Acid/pharmacokinetics , Polyglycolic Acid/pharmacology , RNA, Neoplasm/chemistry , RNA, Neoplasm/pharmacokinetics , RNA, Neoplasm/pharmacology , T-Lymphocytes, Cytotoxic/immunologyABSTRACT
The prickly nanodiamonds easily entered cells via endocytosis followed by unique intracellular translocation characteristicsquick endosomal escape followed by stable residence in cytoplasm. Endosomal membrane rupturing is identified as the major route of nanodiamonds' escaping the vesicle confinement and to the cytoplasm. Little cytotoxicity is observed to associate with the nanodiamonds' cytosolic release. Such features enable its application for gene delivery, which requires both effective cellular uptake and cytosolic release of the gene. Taking green fluorescent protein gene as an example, we demonstrate the successful cytosolic delivery and expression of such a gene using the prickly nanodiamonds as carrier.
