Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Al-Dawadmi Campus, Al-Dawadmi, 11961, Saudi Arabia.
Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7718175911, Iran.
Pharm Res. 2024 Jun;41(6):1163-1181. doi: 10.1007/s11095-024-03722-1. Epub 2024 Jun 5.
This study aims to utilize PEGylated poly (lactic-co-glycolic acid) (PLGA) nanoparticles as a delivery system for simultaneous administration of the BRAF 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-BRAF nanoparticles were synthesized using a PLGA-PEG-PLGA tri-block copolymer, BRAF, 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 and PLGA-IMQ-BRAF nanoparticles in inhibiting subcutaneous BPD6 tumor growth.
The results highlight the successful synthesis of PEG-PLGA-IMQ-BRAF nanoparticles (203 ± 11.1 nm), releasing 73.4% and 63.2% of IMQ and BARF, 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. Moreover, PEG-PLGA-IMQ-BRAF 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 and PLGA-IMQ-BRAF. In vivo, PEG-PLGA-IMQ-BRAF 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.
本研究旨在利用聚乙二醇化聚（乳酸-共-乙醇酸）（PLGA）纳米粒作为一种递送系统，同时给予 BRAF 肽（一种肿瘤特异性抗原）和咪喹莫特（IMQ）。目的是刺激树突状细胞（DC）成熟，激活巨噬细胞，并促进 C57BL6 小鼠中的抗原呈递。
使用 PLGA-PEG-PLGA 三嵌段共聚物、BRAF 和 IMQ 合成 PEG-PLGA-IMQ-BRAF 纳米粒。通过大小测量和药物释放分析对其进行表征。通过 MTT 和 ELISA 测定评估其抑制 BPD6 黑色素瘤细胞生长和激活未成熟骨髓 DC、T 细胞、巨噬细胞和脾细胞的功效。在体内，通过比较其与 IMQ+BRAF 和 PLGA-IMQ-BRAF 纳米粒在抑制皮下 BPD6 肿瘤生长方面的治疗和免疫原性潜力，评估其潜在的治疗和免疫原性。
结果突出了成功合成的 PEG-PLGA-IMQ-BRAF 纳米粒（203±11.1nm），在最初的 48 小时内分别释放 73.4%和 63.2%的 IMQ 和 BARF。体外实验中，这些纳米粒对 BPD6 细胞的效力提高了 1.3 倍，与 PLGA-IMQ-BRAF 相比，细胞毒性增强了 2.8 倍。此外，PEG-PLGA-IMQ-BRAF 增强了 IMQ 细胞毒性作用的效力，使 DC、T 细胞、巨噬细胞和脾细胞的激活分别增加了 1.3 倍至~2.4 倍，与 IMQ-BRAF 和 PLGA-IMQ-BRAF 相比。在体内，与其他制剂相比，PEG-PLGA-IMQ-BRAF 抑制皮下 BPD6 肿瘤生长的效力提高了 1.3 至 7.5 倍。
研究结果表明，PEG-PLGA 纳米粒能有效促进 DC 成熟、T 细胞激活，并可能促进巨噬细胞激活。该研究突出了这种纳米复合物在疫苗开发中的应用前景。
