Functionalized Multi-Walled Carbon Nanotubes for Targeting Delivery of Immunostimulatory CpG Oligonucleotides Against Prostate Cancer
Functionalized Multi-Walled Carbon Nanotubes for Targeting Delivery of Immunostimulatory CpG Oligonucleotides Against Prostate Cancer
复制标题
用于靶向递送针对前列腺癌的免疫刺激性 CpG 寡核苷酸的功能化多壁碳纳米管
DOI：
10.1166/jbn.2018.2605
复制
发表时间：
2018
影响因子：
2.9
通讯作者：
Gao Yuan
中科院分区：
文献类型：
--
作者：
Xia Qingming;Gong Chunai;Gu Fenfen;Wang Zhuo;Hu Chuling;Zhang Lijuan;Qiang Lei;Ding Xueying;Gao Shen;Gao Yuan
基于免疫的肿瘤治疗已成功用于癌症治疗。本研究基于多壁碳纳米管（MWCNTs）结合H3 R6多肽（MHR-CpG）构建了一种含非甲基化CpG基序的寡核苷酸（ODNs）纳米给药系统，用于前列腺癌免疫治疗。体外和体内毒性试验结果表明，所制备的MHR具有良好的生物相容性。共聚焦激光扫描显微镜证实MHR-CpG可以特异性靶向内体TLR 9。此外，MHR的使用增强了CpG在体液和细胞免疫途径中的免疫原性，如CD 4 + T细胞、CD 8 + T细胞、TNF-α和IL-6的表达增加所证明的。对RM-1荷瘤小鼠的体内抗癌功效研究表明，MHR-CpG可将免疫治疗剂递送至肿瘤部位和肿瘤引流淋巴结以抑制肿瘤生长。这些结果表明，MHR-CpG是一个有前途的多功能纳米系统，用于前列腺癌的免疫治疗。
Immuno-based oncotherapy has been successfully implemented for cancer treatment. In the present study, we developed a Oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs (CpG ODNs) nano-delivery system based on Multi-walled carbon nanotubes (MWCNTs) conjugated with H3R6 polypeptide (MHR-CpG) for prostate cancer immunotherapy. The in vitro and in vivo toxicity data revealed that the prepared MHR showed high biocompatibility. Confocal laser scanning microscopy confirmed that MHR-CpG could specifically target the endosomal TLR9. In addition, the use of MHR enhanced the immunogenicity of CpG in both humoral and cellular immune pathways, as evidenced by the increased expression of CD4+ T-cells, CD8+ T-cells, TNF-α, and IL-6. The in vivo anti-cancer efficacy study on RM-1 tumor-bearing mice demonstrated that MHR-CpG could deliver the immunotherapeutics to the tumor site and the tumor-draining lymph node to suppress tumor growth. These results suggested that MHR-CpG was a promising multifunctional nano system for prostate cancer immunotherapy.