Vx3-Functionalized Alumina Nanoparticles Assisted Enrichment of Ubiquitinated Proteins from Cancer Cells for Enhanced Cancer Immunotherapy
Vx3-Functionalized Alumina Nanoparticles Assisted Enrichment of Ubiquitinated Proteins from Cancer Cells for Enhanced Cancer Immunotherapy
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Vx3 功能化氧化铝纳米颗粒辅助富集癌细胞中的泛素化蛋白，以增强癌症免疫治疗
DOI：
10.1021/acs.bioconjchem.7b00578
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发表时间：
2018
影响因子：
4.7
通讯作者：
Wang Li xin
中科院分区：
文献类型：
--
作者：
Zhao Jinjin;Pan Nin;Huang Fang;Aldarouish Mohanad;Wen Zhifa;Gao Rong;Zhang Yuye;Hu Hong Ming;Shen Yanfei;Wang Li xin
利用α-Al_2O_3纳米粒子与泛素结合蛋白(α-Al_2O_3-Vx_3)通过化学连接物共价连接，开发了一种简单而有效的策略来从癌细胞裂解液中富集泛素化蛋白(UPS)。功能化的α-Al_2O_3-VX_3对癌细胞裂解液中的UPS具有长期稳定和高效的富集性。流式细胞仪分析结果表明，树突状细胞(DC)吞噬共价连接的α-Al_2O_3-V_x3-UP比α-Al_2O_3和V_x3-UP的物理混合物(α-Al_2O_3/V_x3-UP)更有效。激光共聚焦显微镜图像显示α-Al_2O_3-Vx3-UP定位于DC的自噬小体内，然后以自噬相关的交叉递呈途径将α-Al_2O_3-Vx_3-UP交叉递呈给CD8+T细胞。此外，α-Al_2O_3-Vx3-UPS比α-Al_2O_3/细胞裂解物或α-Al_2O_3/Vx_3-UPS更能增强抗肿瘤免疫应答和抗肿瘤效应。这项工作突出了利用Vx3共价连接的α-Al_2O_3作为一种简单而有效的平台来从癌细胞中浓缩UP用于开发高效治疗性癌症疫苗的潜力。
A simple and effective strategy was developed to enrich ubiquitinated proteins (UPs) from cancer cell lysate using the α-Al2O3nanoparticles covalently linked with ubiquitin binding protein (Vx3) (denoted as α-Al2O3–Vx3) via a chemical linker. The functionalized α-Al2O3–Vx3 showed long-term stability and high efficiency for the enrichment of UPs from cancer cell lysates. Flow cytometry analysis results indicated dendritic cells (DCs) could more effectively phagocytize the covalently linked α-Al2O3–Vx3-UPs than the physical mixture of α-Al2O3and Vx3-UPs (α-Al2O3/Vx3-UPs). Laser confocal microscopy images revealed that α-Al2O3–Vx3-UPs localized within the autophagosome of DCs, which then cross-presented α-Al2O3–Vx3-UPs to CD8+T cells in an autophagosome-related cross-presentation pathway. Furthermore, α-Al2O3–Vx3-UPs enhanced more potent antitumor immune response and antitumor efficacy than α-Al2O3/cell lysate or α-Al2O3/Vx3-UPs. This work highlights the potential of using the Vx3 covalently linked α-Al2O3as a simple and effective platform to enrich UPs from cancer cells for the development of highly efficient therapeutic cancer vaccines.