Wang Xiaoxiao, Li Binhan, Jing Huimin, Dong Xia, Leng Xigang
Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, P. R. China.
J Mater Chem B. 2020 May 21;8(19):4245-4258. doi: 10.1039/c9tb02238d. Epub 2020 Apr 13.
Melanoma, the most aggressive skin cancer with a high metastatic index, causes almost 90% of skin cancer mortality. Currently available conservative therapies, including chemotherapy, radiotherapy and immunotherapy, have shown little effect against metastatic melanoma, leading to a very poor prognosis. The present study was aimed at developing a more efficient therapeutic strategy by combining MWCNT mediated photothermal ablation with both chemotherapy and immunotherapy. For this purpose, DOX and CpG were loaded onto MWCNTs via physical adhesion. The diameters of the resultant MWCNT-CpG and MWCNT-DOX were 197.3 ± 5.45 nm and 263.8 ± 7.36 nm, with zeta potentials of -48 ± 4.93 mV and 58 ± 2.42 mV, respectively. Loading with either CpG or DOX significantly enhanced the water dispersibility of the MWCNTs and showed no obvious impact on the physical structure of the MWCNTs. MWCNT loading facilitated the uptake of CpG by bone marrow derived dendritic cells (BMDCs), as well as the maturation of BMDCs. Intratumoral injection of MWCNT-DOX and MWCNT-CpG with subsequent NIR irradiation resulted in a significant delay in tumor progression in melanoma bearing mice, along with an increased number of CD4 and CD8 T cells in the spleen, draining lymph nodes and tumor tissues. The regimen promoted TAM shifting from M2 to M1 while decreasing the number of Treg cells in the tumor microenvironment, which probably contributed to the enhanced anti-tumor efficacy of the regimen. Hopefully, the invented strategy might find potential applications for the therapy of melanoma in the future.
黑色素瘤是最具侵袭性的皮肤癌，转移指数高，导致近90%的皮肤癌死亡。目前可用的保守疗法，包括化疗、放疗和免疫疗法，对转移性黑色素瘤效果甚微，预后很差。本研究旨在通过将多壁碳纳米管介导的光热消融与化疗和免疫疗法相结合，开发一种更有效的治疗策略。为此，通过物理吸附将阿霉素（DOX）和CpG负载到多壁碳纳米管上。所得的多壁碳纳米管-CpG和多壁碳纳米管-DOX的直径分别为197.3±5.45纳米和263.8±7.36纳米，ζ电位分别为-48±4.93毫伏和58±2.42毫伏。负载CpG或DOX均显著提高了多壁碳纳米管的水分散性，且对多壁碳纳米管的物理结构无明显影响。多壁碳纳米管负载促进了骨髓来源的树突状细胞（BMDCs）对CpG的摄取以及BMDCs的成熟。瘤内注射多壁碳纳米管-DOX和多壁碳纳米管-CpG并随后进行近红外照射，导致荷黑色素瘤小鼠的肿瘤进展显著延迟，同时脾脏、引流淋巴结和肿瘤组织中的CD4和CD8 T细胞数量增加。该方案促进肿瘤相关巨噬细胞（TAM）从M2型向M1型转变，同时减少肿瘤微环境中调节性T细胞（Treg）的数量，这可能有助于增强该方案的抗肿瘤疗效。有望该发明的策略在未来黑色素瘤治疗中找到潜在应用。
