Effective CpG Delivery Using Zwitterion-Functionalized Dendrimer-Entrapped Gold Nanoparticles to Promote T Cell-Mediated Immunotherapy of Cancer Cells.
Effective CpG Delivery Using Zwitterion-Functionalized Dendrimer-Entrapped Gold Nanoparticles to Promote T Cell-Mediated Immunotherapy of Cancer Cells.
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使用两性离子功能化树枝状大分子包埋的金纳米颗粒进行有效的 CpG 递送，以促进 T 细胞介导的癌细胞免疫治疗
DOI：
10.3390/bios12020071
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发表时间：
2022-01-27
期刊：
影响因子：
--
通讯作者：
Cao X
中科院分区：
文献类型：
--
作者：
Chen H;Zhang Y;Li L;Guo R;Shi X;Cao X
近年来，基于细胞的免疫疗法已成为彻底消除癌症最有希望的方法之一。主要挑战是有效促进适当的免疫反应，通过激活的 T 细胞杀死癌细胞。本研究调查了由 Au DENPs-MPC（两性离子 2-甲基丙烯酰氧基乙基磷酰胆碱 (MPC) 功能化树枝状大分子包埋的金纳米颗粒）加载未甲基化胞嘧啶鸟嘌呤二核苷酸 (CPG) 的寡聚脱氧核苷酸 (ODN) 触发的 T 细胞介导的免疫疗法的效果。在这里，我们首先合成了Au DENPs-MPC，评估了它们压缩CpG-ODN并将其转染至骨髓树突状细胞（BMDC）的能力，并研究了利用成熟BMDC刺激的T细胞抑制肿瘤细胞生长的潜力。所开发的 Au DENPs-MPC 可以明显降低 Au DENPs 的毒性，并增强 CpG-ODN 向 BMDC 的转移以使其成熟，不同表面成熟标记物增加了 44.41-48.53%。 Transwell实验证明离体激活的T细胞表现出优异的抗肿瘤能力，可以有效抑制肿瘤细胞的生长。这些结果表明Au DENPs-MPC可以有效地递送CpG-ODN，增强BMDC激活T细胞的抗原呈递能力，这表明负载CpG-ODN的Au DENPs-MPC介导的基于T细胞的免疫治疗可能成为最有前途的癌症治疗方法。
Recently, cell-based immunotherapy has become one of the most promising ways to completely eliminate cancer. The major challenge is to effectively promote a proper immune response to kill the cancer cells by activated T cells. This study investigated the effect of T cell-mediated immunotherapy trigged by Au DENPs-MPC (zwitterion 2-methacryloyloxyethyl phosphorylcholine (MPC)-functionalized dendrimer-entrapped gold nanoparticles) loading oli-godeoxynucleotides (ODN) of unmethylated cytosine guanine dinucleotide (CPG). Here, we first synthesized Au DENPs-MPC, evaluated their capability to compress and transfect CpG-ODN to bone marrow dendritic cells (BMDCs), and investigated the potential to use T cells stimulated by matured BMDCs to inhibit the growth of tumor cells. The developed Au DENPs-MPC could apparently reduce the toxicity of Au DENPs, and enhanced transfer CpG-ODN to the BMDCs for the maturation as demonstrated by the 44.41–48.53% increase in different surface maturation markers. The transwell experiments certificated that ex vivo activated T cells display excellent anti-tumor ability, which could effectively inhibit the growth of tumor cells. These results suggest that Au DENPs-MPC can deliver CpG-ODN efficiently to enhance the antigen presentation ability of BMDCs to activate T cells, indicating that T cells-based immunotherapy mediated by Au DENPs-MPC loaded with CpG-ODN may become the most promising treatment of cancer.
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影响因子：
11.5
作者：
Bol, Kalijn F.;Schreibelt, Gerty;Figdor, Carl G.
通讯作者：
Figdor, Carl G.
影响因子：
5.5
作者：
Majoros, IJ;Keszler, B;Baker, JR
通讯作者：
Baker, JR
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
2.2
作者：
Lutz, MB;Kukutsch, N;Schuler, G
通讯作者：
Schuler, G
影响因子：
3.8
作者：
Braun, CS;Vetro, JA;Middaugh, CR
通讯作者：
Middaugh, CR