Yu Ruihong, Song Zuchen, Jin Lan, Jiao Lina, Liu Huina, Zhang Shun, Hu Yaoren, Sun Yuechao, Li Entao, Zhao Guofang, Liu Zhenguang, Cai Ting
Ningbo No. 2 Hospital, Ningbo 315010, Zhejiang, China; Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo 315000, Zhejiang, China; College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
Ningbo No. 2 Hospital, Ningbo 315010, Zhejiang, China; College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
Int J Biol Macromol. 2025 Mar;292:139157. doi: 10.1016/j.ijbiomac.2024.139157. Epub 2024 Dec 24.
Functional modification of drugs can significantly improve their efficacy and safety, thus enabling targeted therapy. Functional modifications based on polysaccharides can alter their molecular structure, and effectively enhance their functional properties and biological activities. Herein, we designed and synthesized cationic Laminarin (CLam) modified with polyethyleneimine (PEI) and explored its application as a vaccine adjuvant. The PEI modification resulted in a positively charged surface of CLam, which was mixed with model antigen (Ovalbumin, OVA) to form CLam/OVA nanoparticles with an optimal particle size of about 380.07 nm, a uniform distribution of the particle size and a stable system. In vitro experiments showed that the positive charge on the surface of CLam/OVA enabled it to be effectively internalized by bone marrow dendritic cells (BMDCs), promoted cell maturation, lysosomal escape, and the efficiency of antigen cross-presentation. Mechanically, CLam/OVA induces BMDC function via toll-like receptors, cytokine receptors, and chemokine-mediated signaling pathways. CLam/OVA induced stronger humoral and cellular immunity compared to the aluminum adjuvant. CLam/OVA induces higher levels of OVA-specific antibodies, generates cytotoxic T lymphocyte immune responses, and stimulates IFN-γ secretion. Overall, this study demonstrates that functionalization is critical for the rational design of polysaccharides to boost antigen-specific immune responses for more effective and long-lasting vaccination.
药物的功能修饰可显著提高其疗效和安全性，从而实现靶向治疗。基于多糖的功能修饰可改变其分子结构，并有效增强其功能特性和生物活性。在此，我们设计并合成了用聚乙烯亚胺（PEI）修饰的阳离子海带多糖（CLam），并探索了其作为疫苗佐剂的应用。PEI修饰使CLam表面带正电荷，将其与模型抗原（卵清蛋白，OVA）混合形成CLam/OVA纳米颗粒，其最佳粒径约为380.07nm，粒径分布均匀，体系稳定。体外实验表明，CLam/OVA表面的正电荷使其能够被骨髓树突状细胞（BMDCs）有效内化，促进细胞成熟、溶酶体逃逸以及抗原交叉呈递效率。从机制上讲，CLam/OVA通过Toll样受体、细胞因子受体和趋化因子介导的信号通路诱导BMDC功能。与铝佐剂相比，CLam/OVA诱导更强的体液免疫和细胞免疫。CLam/OVA诱导更高水平的OVA特异性抗体，产生细胞毒性T淋巴细胞免疫反应，并刺激IFN-γ分泌。总体而言，本研究表明功能化对于合理设计多糖以增强抗原特异性免疫反应以实现更有效和持久的疫苗接种至关重要。
