Developing Engineered Nano-Immunopotentiators for the Stimulation of Dendritic Cells and Inhibition and Prevention of Melanoma

• DOI: 10.1007/s11095-024-03722-1
• Publication Date: 2024-06-05T22:03:10Z
• Authors: Sitah Alharthi; Seyed Zeinab Alavi; Mehr un Nisa; Maedeh Koohi; Aun Raza; Hasan Ebrahimi Sh...; Seyed Ebrahim Alavi
• Keywords: Proto-Oncogene Proteins B-raf; Imiquimod; Skin Neoplasms; Macrophages; Dendritic Cells; Polyethylene Glycols; Mice, Inbred C57BL; Mice; Drug Liberation; Adjuvants, Immunologic; Polylactic Acid-Polyglycolic Acid Copolymer; Cell Line, Tumor; Animals; Nanoparticles; Humans; Female; Melanoma

This study aims to utilize PEGylated poly (lactic-co-glycolic acid) (PLGA) nanoparticles as a delivery system for simultaneous administration of the BRAFV600E peptide, a tumor-specific antigen, and imiquimod (IMQ). The objective is to stimulate dendritic cell (DC) maturation, activate macrophages, and facilitate antigen presentation in C57BL6 mice.PEG-PLGA-IMQ-BRAFV600E nanoparticles were synthesized using a PLGA-PEG-PLGA tri-block copolymer, BRAFV600E, and IMQ. Characterization included size measurement and drug release profiling. Efficacy was assessed in inhibiting BPD6 melanoma cell growth and activating immature bone marrow DCs, T cells, macrophages, and splenocyte cells through MTT and ELISA assays. In vivo, therapeutic and immunogenic effects potential was evaluated, comparing it to IMQ + BRAFV600E and PLGA-IMQ-BRAFV600E nanoparticles in inhibiting subcutaneous BPD6 tumor growth.The results highlight the successful synthesis of PEG-PLGA-IMQ-BRAFV600E nanoparticles (203 ± 11.1 nm), releasing 73.4% and 63.2% of IMQ and BARFV600E, respectively, within the initial 48 h. In vitro, these nanoparticles demonstrated a 1.3-fold increase in potency against BPD6 cells, achieving ~ 2.8-fold enhanced cytotoxicity compared to PLGA-IMQ-BRAFV600E. Moreover, PEG-PLGA-IMQ-BRAFV600E exhibited a 1.3-fold increase in potency for enhancing IMQ cytotoxic effects and a 1.1- to ~ 2.4-fold increase in activating DCs, T cells, macrophages, and splenocyte cells compared to IMQ-BRAFV600E and PLGA-IMQ-BRAFV600E. In vivo, PEG-PLGA-IMQ-BRAFV600E displayed a 1.3- to 7.5-fold increase in potency for inhibiting subcutaneous BPD6 tumor growth compared to the other formulations.The findings suggest that PEG-PLGA nanoparticles effectively promote DC maturation, T cell activation, and potentially macrophage activation. The study highlights the promising role of this nanocomposite in vaccine development.