Developing Engineered Nano-Immunopotentiators for the Stimulation of Dendritic Cells and Inhibition and Prevention of Melanoma.
Pharm Res
; 41(6): 1163-1181, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38839718
ABSTRACT
OBJECTIVE:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
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Células Dendríticas
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Proteínas Proto-Oncogénicas B-raf
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Nanopartículas
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Imiquimod
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Melanoma
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Ratones Endogámicos C57BL
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Pharm Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
Arabia Saudita