Alrahimi Jehan S, Alotaibi Najla S, Aldahlawi Alia M, Basingab Fatemah S, Zaher Kawther A
Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Vaccines (Basel). 2025 Apr 28;13(5):474. doi: 10.3390/vaccines13050474.
Dendritic cells (DCs) are major contributors to generating an effective immune response due to their ability to present antigens to T cells. Recently, nanoparticles have been widely used in different medical applications, such as drug-delivery systems, to enhance the function of impaired immune cells. This research aims to develop an effective antitumor DC-based vaccine by adsorption of chitosan-nanoparticles (CH-NPs) onto DCs. Undifferentiated mouse bone marrow progenitor cells were differentiated into mature DCs using cytokines and lipopolysaccharides. CH-NPs were prepared using the ionic gelation method and subsequently used to coat the stimulated DCs. The MTT assay was employed to assess the cytotoxicity of all formulations. To compare the antitumor effect of CH-NPs, DCs, and DCs-CH-NPs, mice were divided into five groups and injected with the respective vaccine formulations. Following immunization, flow cytometry was used to analyze DC and CD4 T cell activation in blood and spleen tissues. Histological samples from the spleen and lymph nodes were also collected. Our findings show that co-stimulatory molecules CD80/CD86 and the DC maturation marker CD83 were upregulated in the vaccinated DCs, indicating their maturation. Moreover, CD83, CD11c, and MHC-II were upregulated in blood and spleen samples in vivo. The DC-CH-NPs vaccinated group had a higher mean percentage of CD83 expression in blood samples (76.7 ± 17.1) compared to the DCs group (47.7 ± 11.0) and the CH-NPs group (37.7 ± 8.6). DC markers, particularly CD83, were highly expressed in spleen samples. Additionally, the DC-CH-NPs vaccinated group had a significantly higher number of CD4 T cells (MFI = 26.1 ± 2.3) compared to the DCs (18.6 ± 1.6) and CH-NPs (13.3 ± 1.4) groups. The present study concludes that the DC-CH-NPs vaccine formulation can induce a potent in vivo immune response. These data may provide valuable insights for developing effective delivery systems for antitumor vaccines.
树突状细胞（DCs）由于能够向T细胞呈递抗原，是产生有效免疫反应的主要贡献者。最近，纳米颗粒已广泛应用于不同的医学应用中，如药物递送系统，以增强受损免疫细胞的功能。本研究旨在通过将壳聚糖纳米颗粒（CH-NPs）吸附到DCs上来开发一种有效的基于DC的抗肿瘤疫苗。使用细胞因子和脂多糖将未分化的小鼠骨髓祖细胞分化为成熟的DCs。采用离子凝胶法制备CH-NPs，随后用于包被受刺激的DCs。采用MTT法评估所有制剂的细胞毒性。为了比较CH-NPs、DCs和DCs-CH-NPs的抗肿瘤效果，将小鼠分为五组，并注射相应的疫苗制剂。免疫后，使用流式细胞术分析血液和脾脏组织中的DC和CD4 T细胞活化情况。还收集了脾脏和淋巴结的组织学样本。我们的研究结果表明，共刺激分子CD80/CD86和DC成熟标志物CD83在接种疫苗的DCs中上调，表明它们成熟。此外，体内血液和脾脏样本中CD83、CD11c和MHC-II上调。与DCs组（47.7±11.0）和CH-NPs组（37.7±8.6）相比，DC-CH-NPs接种组血液样本中CD83表达的平均百分比更高（76.7±17.1）。DC标志物，特别是CD83，在脾脏样本中高度表达。此外，与DCs组（18.6±1.6）和CH-NPs组（13.3±1.4）相比，DC-CH-NPs接种组的CD4 T细胞数量明显更多（MFI = 26.1±2.3）。本研究得出结论，DC-CH-NPs疫苗制剂可在体内诱导强烈的免疫反应。这些数据可能为开发有效的抗肿瘤疫苗递送系统提供有价值的见解。
