研究动态
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使用模拟甘露糖的糖聚合物纳米颗粒增强癌症免疫治疗可诱导树突状细胞的激活。

Enhancing cancer immunotherapy with mannose mimicking glycopolymer nanoparticles induced activation of Dendritic cells.

发表日期:2024 Aug 10
作者: Keerti Bhamidipati, Naga Malleswara Rao Nakka, Mariam Ahmed, Kalpana Javvaji, Rajkumar Banerjee, Nagaprasad Puvvada, Annadanam V Sesha Sainath, Sumana Chakravarty
来源: BIOORGANIC CHEMISTRY

摘要:

癌症免疫疗法利用免疫系统的固有能力来对抗恶性肿瘤。然而,由于树突状细胞(DC)的分布有限和免疫抑制的肿瘤微环境,有效刺激树突状细胞具有挑战性。因此,靶向在树突状细胞上高表达的甘露糖受体是一种有前途的策略。本研究研究了基于甘露糖的糖聚合物纳米颗粒的开发,以通过增强抗原呈递来诱导树突状细胞的激活。合成了一种模拟甘露糖的新型 ABA 型三嵌段生物共轭糖聚合物 (PMn-b-PCL-b-PMn)。这种聚合物进一步用二十六烷基二甲基溴化铵 (DHDAB) 进行修饰,以制备用于 pCMV-TRP2(黑色素瘤和胶质母细胞瘤的抗原标记)基因传递的阳离子纳米粒子 (CMNP)。将 CMNP 和 CMNP-TRP2 复合物产生的免疫反应与小鼠皮下注射后未处理的对照进行比较。注射后细胞分析显示,次级淋巴器官(包括脾脏和淋巴结)中 DC 激活强劲,T 细胞数量增加。这些研究结果表明,CMNP 可以作为一种有效的仿生癌症疫苗接种载体,通过靶向树突状细胞激活来增强免疫反应。版权所有 © 2024 Elsevier Inc. 保留所有权利。
Cancer immunotherapy leverages the immune system's inherent capacity to combat malignancies. However, effective stimulation of Dendritic cells (DCs) is challenging due to their limited distribution and the immune-suppressive tumor microenvironment. Thus, targeting mannose receptors, which are highly expressed on DCs, represents a promising strategy. This study investigates the development of mannose-based glycopolymer nanoparticles to induce activation of DCs through enhanced antigen presentation. A novel ABA-type triblock bioconjugated glycopolymer (PMn-b-PCL-b-PMn), which mimics mannose was synthesized. This polymer was further modified with Dihexadecyldimethylammonium bromide (DHDAB) to prepare cationic nanoparticles (CMNP) for gene delivery of pCMV-TRP2, an antigenic marker for both melanoma and glioblastoma. The immune response generated by CMNP and the CMNP-TRP2 polyplex was compared to an untreated control following subcutaneous injection in mice. Post-injection cytometric analysis revealed robust DC activation and increased T-cell populations in secondary lymphoid organs, including the spleen and lymph nodes. These findings suggest that CMNP can serve as a potent biomimicking vaccination vehicle against cancer, enhancing the immune response through targeted DCs activation.Copyright © 2024 Elsevier Inc. All rights reserved.