State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
J Mater Chem B. 2020 Jun 21;8(23):5052-5063. doi: 10.1039/d0tb00678e. Epub 2020 May 13.
The major obstacle that hinders current cancer immunotherapies is the development of an effective approach to promote a proper immune response for effective tumor killing through activated T cells. Herein, we report an effective T cell-based tumor immunotherapy approach through nonviral delivery of a cytosine-guanine (CpG) oligonucleotide using dendrimer-entrapped gold nanoparticles (Au DENPs). In our work, Au DENPs partially decorated with methoxy polyethylene glycol (mPEG) were synthesized and characterized to be used as a vector for CpG delivery to bone marrow-derived dendritic cells (BMDCs). The BMDCs matured via CpG delivery were used to activate T cells for adoptive immunotherapy of cancer cells. We show that the developed PEGylated Au DENPs are able to effectively transfect CpG leading to the maturation of BMDCs that can be used to activate T cells for subsequent adoptive immunotherapy of cancer cells in vitro and a xenografted melanoma tumor model in vivo after intravenous injection. Importantly, the developed approach to genetically engineer BMDCs enables a triggered adaptive immune response and memory of T cells, which can be beneficial for effective inhibition of tumor metastasis and recurrence. The developed nonviral gene delivery approach using Au DENPs as a vector for T cell-based immunotherapy can be applied to different cancer types.
目前癌症免疫疗法的主要障碍是开发一种有效的方法，通过激活 T 细胞来促进适当的免疫反应以有效杀伤肿瘤。在此，我们通过使用树状聚合物包裹的金纳米粒子（Au DENPs）非病毒传递胞嘧啶-鸟嘌呤（CpG）寡核苷酸，报告了一种有效的基于 T 细胞的肿瘤免疫治疗方法。在我们的工作中，部分用甲氧基聚乙二醇（mPEG）修饰的 Au DENPs 被合成并进行了表征，用作 CpG 递送至骨髓来源树突状细胞（BMDCs）的载体。通过 CpG 传递成熟的 BMDCs 用于激活 T 细胞，以进行癌细胞的过继免疫治疗。我们表明，开发的聚乙二醇化 Au DENPs 能够有效地转染 CpG，导致 BMDCs 的成熟，可用于体外激活 T 细胞，然后在静脉注射后进行过继免疫治疗异种移植黑色素瘤肿瘤模型。重要的是，该方法通过基因工程改造 BMDCs 可引发适应性免疫反应和 T 细胞记忆，这对有效抑制肿瘤转移和复发可能是有益的。该方法使用 Au DENPs 作为基于 T 细胞的免疫疗法的载体进行非病毒基因传递，可应用于不同类型的癌症。
