Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine

• Published in: International journal of nanomedicine Vol. 13; pp. 367 - 386
• Main Authors: Jahan, Sheikh Tasnim, Sadat, Sams Ma, Haddadi, Azita
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Acids; Adsorption; Albumin; Analysis; anti-CD205; Antigen presentation; Antigens; Biomedical materials; Cancer research; Cancer therapies; Cancer vaccines; Clinical trials; Dendritic cells; Immune response; Immune system; Immunology; Immunotherapy; Lipids; Lymphocytes; Major histocompatibility complex; MPLA; Nanoparticle; Nanoparticles; Original Research; Ovalbumin; Pharmacy; PLGA; Polymer industry; Polymers; Polyvinyl alcohol; Proteins; T cells; Tumor necrosis factor-TNF; Tumors; Vaccines; United States > US; nanoparticle; dendritic cells; monophosphoryl lipid A; immunotherapy; ovalbumin
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S144266

The aim of this research was to develop a targeted antigen-adjuvant assembled delivery system that will enable dendritic cells (DCs) to efficiently mature to recognize antigens released from tumor cells. It is important to target the DCs with greater efficiency to prime T cell immune responses. In brief, model antigen, ovalbumin (OV), and monophosphoryl lipid A adjuvant were encapsulated within the nanoparticle (NP) by double emulsification solvent evaporation method. Targeted NPs were obtained through ligand incorporation via physical adsorption or chemical conjugation process. Intracellular uptake of the NPs and the maturation of DCs were evaluated with flow cytometry. Remarkably, the developed delivery system had suitable physicochemical properties, such as particle size, surface charge, OV encapsulation efficiency, biphasic OV release pattern, and safety profile. The ligand modified formulations had higher targeting efficiency than the non-tailored NPs. This was also evident when the targeted formulations expressed comparatively higher fold increase in surface activation markers such as CD40, CD86, and major histocompatibility complex class II molecules. The maturation of DCs was further confirmed through secretion of extracellular cytokines compared to control cells in the DC microenvironment. Physicochemical characterization of NPs was performed based on the polymer end groups, their viscosities, and ligand-NP bonding type. In conclusion, the DC stimulatory response was integrated to develop a relationship between the NP structure and desired immune response. Therefore, the present study narrates a comparative evaluation of some selected parameters to choose a suitable formulation useful for in vivo cancer immunotherapy.