Enhancement of Anti-Tumor Effect of Particulate Vaccine Delivery System by ‘Bacteriomimetic’ CpG Functionalization of Poly-Lactic-Co-glycolic Acid Nanoparticles

Abstract

Aim Low immunogenicity remains a major obstacle in realizing the full potential of cancer vaccines. In this study, we evaluated CpG-coated tumor antigen (Tag)-encapsulating ‘bacteriomimetic’ nanoparticles (CpG-nanoparticle [NP]-Tag NPs) as an approach to enhance anti-tumor immunity. Materials & methods CpG-NP-Tag NPs were synthesized, characterized for their physicochemical properties and tested in vivo. Results We found CpG predosing followed by intraperitoneal (IP) immunization with CpG-NP-Tag NPs significantly attenuated tumor growth in female BALB/c mice compared with respective controls. Histopathological and Immunofluorescence data revealed CpG-NP-Tag tumors had lower proliferation, higher apoptotic activity, greater CD4+ and CD8+ T cell infiltration as well as higher IFN-γ levels as compared with control groups. Conclusion Our findings suggest CpG-NP-Tag NPs can enhance anti-tumor effect of nanoparticulate tumor vaccination system.

Rationalizing the Use of Functionalized Poly-Lactic-Co-Glycolic Acid Nanoparticles for Dendritic Cell-Based Targeted Anticancer Therapy

“…Various antigenic substances (proteins, peptides, plasmid DNA, viruses) have been successfully delivered using PLGA particles and therefore are good candidates for vaccine delivery. Our group recently published a study demonstrating the antitumor effects of PLGA-based CpG-coated Tag encapsulated (CpG-NP-Tag) NPs after in vivo administration in a prophylactic setting [9]. In the current manuscript, we show ex vivo studies using CpG-NP-Tag NPs with BMDCs to identify the feasibility of such construct on antitumor action at the level of the APC.…”

“…Syngeneic breast Cancer BALB/c Mice Model and Figure 2. We monitored tumor growth using vernier caliper (Rate of Tumor Growthand Animal Weight) at different time points until day 21 and found attenuation of tumor growth ( Supplementary Figure S1) as in our previously published studies [9]. After euthanasia of mice, tumors, spleens and serum were collected for further analysis of immunostimulatory functions of CpG-NP-Tag NPs.…”

“…CpG-NP-Tag NPs were prepared using water-in-oilin-water (w/o/w) double emulsion method employing solvent evaporation technique reported in our previous studies [9]. Briefly, primary emulsion (w/o) was prepared by vortexing a 200 μl of Tag solution (1 μg/μl) with 1 ml of organic phase (PLGA [70 mg] in ethylacetate [1 ml]).…”

“…Our previous studies show CpG preimmunization preceding CpG-NP-Tag NP immunization promotes enhanced IFN-γ production and CD4 + / CD8 + tumor T-cell infiltration [9]. Thus, we utilized a similar CpG preimmunization scheme for our current studies as described in 'Generation of bone marrow-derived dendritic cells'.…”

“…The main advantage of using PLGA NPs from a vaccine perspective is that they serve as a safe, nontoxic mode of codelivery of Ag and adjuvant for a sustained period of Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy time [6][7][8]. Previous studies conducted and published recently by our group demonstrated that PLGA-based CpG-ODN-coated tumor antigen (Tag) encapsulating (CpG-NP-Tag) NPs were able to inhibit cancer cell, growth, proliferation and promote apoptotic cancer cell death in vivo associated with an increase in both CD4 + and CD8 + T-cell infiltration in tumor tissue [9]. However, further investigation is warranted linking NPs function as an immune-mediated mechanism.…”