Guo Liangran, Yan Daisy D, Yang Dongfang, Li Yajuan, Wang Xiaodong, Zalewski Olivia, Yan Bingfang, Lu Wei
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island , Kingston, Rhode Island 02881, United States.
ACS Nano. 2014 Jun 24;8(6):5670-81. doi: 10.1021/nn5002112. Epub 2014 May 13.
Near-infrared light-responsive inorganic nanoparticles have been shown to enhance the efficacy of cancer photothermal ablation therapy. However, current nanoparticle-mediated photothermal ablation is more effective in treating local cancer at the primary site than metastatic cancer. Here, we report the design of a near-infrared light-induced transformative nanoparticle platform that combines photothermal ablation with immunotherapy. The design is based on chitosan-coated hollow CuS nanoparticles that assemble the immunoadjuvants oligodeoxynucleotides containing the cytosine-guanine (CpG) motifs. Interestingly, these structures break down after laser excitation, reassemble, and transform into polymer complexes that improve tumor retention of the immunotherapy. In this "photothermal immunotherapy" approach, photothermal ablation-induced tumor cell death reduces tumor growth and releases tumor antigens into the surrounding milieu, while the immunoadjuvants potentiate host antitumor immunity. Our results indicated that combined photothermal immunotherapy is more effective than either immunotherapy or photothermal therapy alone against primary treated and distant untreated tumors in a mouse breast cancer model. These hollow CuS nanoparticles are biodegradable and can be eliminated from the body after laser excitation.
近红外光响应性无机纳米粒子已被证明可提高癌症光热消融治疗的疗效。然而，目前纳米粒子介导的光热消融在治疗原发部位的局部癌症方面比转移性癌症更有效。在此，我们报告了一种将光热消融与免疫疗法相结合的近红外光诱导转化纳米粒子平台的设计。该设计基于壳聚糖包被的中空硫化铜纳米粒子，其组装了含有胞嘧啶 - 鸟嘌呤（CpG）基序的免疫佐剂寡脱氧核苷酸。有趣的是，这些结构在激光激发后会分解、重新组装并转化为聚合物复合物，从而提高免疫疗法在肿瘤中的留存率。在这种“光热免疫疗法”方法中，光热消融诱导的肿瘤细胞死亡减少了肿瘤生长并将肿瘤抗原释放到周围环境中，而免疫佐剂则增强了宿主的抗肿瘤免疫力。我们的结果表明，在小鼠乳腺癌模型中，联合光热免疫疗法对原发治疗和远处未治疗的肿瘤比单独的免疫疗法或光热疗法更有效。这些中空硫化铜纳米粒子是可生物降解的，并且在激光激发后可从体内清除。
