Sitah Alharthi, Seyed Zeinab Alavi, Mehr Un Nisa, Maedeh Koohi, Aun Raza, Hasan Ebrahimi Shahmabadi, Seyed Ebrahim Alavi
{"title":"开发用于刺激树突状细胞、抑制和预防黑色素瘤的工程纳米免疫诱导剂。","authors":"Sitah Alharthi, Seyed Zeinab Alavi, Mehr Un Nisa, Maedeh Koohi, Aun Raza, Hasan Ebrahimi Shahmabadi, Seyed Ebrahim Alavi","doi":"10.1007/s11095-024-03722-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aims to utilize PEGylated poly (lactic-co-glycolic acid) (PLGA) nanoparticles as a delivery system for simultaneous administration of the BRAF<sup>V600E</sup> 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.</p><p><strong>Methods: </strong>PEG-PLGA-IMQ-BRAF<sup>V600E</sup> nanoparticles were synthesized using a PLGA-PEG-PLGA tri-block copolymer, BRAF<sup>V600E</sup>, 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 + BRAF<sup>V600E</sup> and PLGA-IMQ-BRAF<sup>V600E</sup> nanoparticles in inhibiting subcutaneous BPD6 tumor growth.</p><p><strong>Results: </strong>The results highlight the successful synthesis of PEG-PLGA-IMQ-BRAF<sup>V600E</sup> nanoparticles (203 ± 11.1 nm), releasing 73.4% and 63.2% of IMQ and BARF<sup>V600E</sup>, 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-BRAF<sup>V600E</sup>. Moreover, PEG-PLGA-IMQ-BRAF<sup>V600E</sup> 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-BRAF<sup>V600E</sup> and PLGA-IMQ-BRAF<sup>V600E</sup>. In vivo, PEG-PLGA-IMQ-BRAF<sup>V600E</sup> displayed a 1.3- to 7.5-fold increase in potency for inhibiting subcutaneous BPD6 tumor growth compared to the other formulations.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1163-1181"},"PeriodicalIF":3.5000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Developing Engineered Nano-Immunopotentiators for the Stimulation of Dendritic Cells and Inhibition and Prevention of Melanoma.\",\"authors\":\"Sitah Alharthi, Seyed Zeinab Alavi, Mehr Un Nisa, Maedeh Koohi, Aun Raza, Hasan Ebrahimi Shahmabadi, Seyed Ebrahim Alavi\",\"doi\":\"10.1007/s11095-024-03722-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>This study aims to utilize PEGylated poly (lactic-co-glycolic acid) (PLGA) nanoparticles as a delivery system for simultaneous administration of the BRAF<sup>V600E</sup> 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.</p><p><strong>Methods: </strong>PEG-PLGA-IMQ-BRAF<sup>V600E</sup> nanoparticles were synthesized using a PLGA-PEG-PLGA tri-block copolymer, BRAF<sup>V600E</sup>, 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 + BRAF<sup>V600E</sup> and PLGA-IMQ-BRAF<sup>V600E</sup> nanoparticles in inhibiting subcutaneous BPD6 tumor growth.</p><p><strong>Results: </strong>The results highlight the successful synthesis of PEG-PLGA-IMQ-BRAF<sup>V600E</sup> nanoparticles (203 ± 11.1 nm), releasing 73.4% and 63.2% of IMQ and BARF<sup>V600E</sup>, 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-BRAF<sup>V600E</sup>. Moreover, PEG-PLGA-IMQ-BRAF<sup>V600E</sup> 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-BRAF<sup>V600E</sup> and PLGA-IMQ-BRAF<sup>V600E</sup>. In vivo, PEG-PLGA-IMQ-BRAF<sup>V600E</sup> displayed a 1.3- to 7.5-fold increase in potency for inhibiting subcutaneous BPD6 tumor growth compared to the other formulations.</p><p><strong>Conclusions: </strong>The findings suggest that PEG-PLGA nanoparticles effectively promote DC maturation, T cell activation, and potentially macrophage activation. 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Developing Engineered Nano-Immunopotentiators for the Stimulation of Dendritic Cells and Inhibition and Prevention of Melanoma.
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.
期刊介绍：
Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to:
-(pre)formulation engineering and processing-
computational biopharmaceutics-
drug delivery and targeting-
molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)-
pharmacokinetics, pharmacodynamics and pharmacogenetics.
Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.
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