State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.
Biosensors (Basel). 2022 Jan 27;12(2):71. doi: 10.3390/bios12020071.
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.
最近，基于细胞的免疫疗法已成为彻底消除癌症的最有前途的方法之一。主要的挑战是通过激活的 T 细胞有效地促进适当的免疫反应来杀死癌细胞。本研究探讨了 Au DENPs-MPC（带内盐 2-甲基丙烯酰氧乙基磷酸胆碱（MPC）功能化树枝状聚合物包裹的金纳米粒子）负载未甲基化胞嘧啶鸟嘌呤二核苷酸（CpG）寡脱氧核苷酸（ODN）引发的 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，评估了它们将 CpG-ODN 压缩和转染到骨髓树突状细胞（BMDC）中的能力，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。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，这表现为不同表面成熟标志物的增加 44.41-48.53%。Transwell 实验证明，体外激活的 T 细胞具有出色的抗肿瘤能力，可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，以增强 BMDC 的抗原呈递能力，从而激活 T 细胞，表明基于 Au DENPs-MPC 负载 CpG-ODN 的 T 细胞免疫疗法可能成为癌症最有前途的治疗方法。
