The greatest contributors to cancer mortality are metastasis and the consequences of its treatment. Here, we present a novel treatment of metastatic breast cancer that combines photothermal therapy with targeted single-walled carbon nanotubes (SWCNTs) and immunostimulation with a checkpoint inhibitor. We find that the selective near-infrared photothermal ablation of primary orthotopic EMT6 breast tumors in syngeneic BALB/cJ mice using an annexin A5 (ANXA5) functionalized SWCNT bioconjugate synergistically enhances an anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4)-dependent abscopal response, resulting in an increased survival (55%) at 100 days after tumor inoculation. In comparison, there was no survival at 100 days for either photothermal therapy by itself or immunostimulation by itself. Prior to photothermal therapy, the SWCNT-ANXA5 bioconjugate was administered systemically at a relatively low dose of 1.2 mg/kg, where it then accumulated in tumor vasculature via ANXA5-dependent binding. During photothermal therapy, the average maximum temperature in the tumor reached 54 °C (duration 175 s). The mechanism of prolonged survival resulting from combinatorial photothermal ablation and immune stimulation was evaluated by flow cytometric quantification of splenic antitumoral immune effector cells and serum cytokine quantification.

癌症死亡的最大原因是转移及其治疗的后果。在这里，我们提出了一种转移性乳腺癌的新型治疗方法，该方法将光热疗法与靶向单壁碳纳米管（SWCNTs）结合起来，并与检查点抑制剂进行免疫刺激相结合。我们发现使用膜联蛋白A5（ANXA5）功能化的SWCNT生物缀合物在同源BALB / cJ小鼠中原发性原位EMT6乳腺肿瘤的选择性近红外光热消融协同增强了抗细胞毒性T淋巴细胞相关蛋白4（抗CTLA- 4）依赖性的绝对反应，导致肿瘤接种100天后存活率提高（55％）。相比之下，光热疗法本身或免疫刺激本身在100天时均无存活。在光热疗法之前，SWCNT-ANXA5生物缀合物以1.2 mg / kg的较低剂量全身给药，然后通过ANXA5依赖性结合在肿瘤脉管系统中积累。在光热疗法期间，肿瘤的平均最高温度达到54°C（持续时间175 s）。通过脾脏抗肿瘤免疫效应细胞的流式细胞术定量和血清细胞因子定量，评估了组合光热消融和免疫刺激导致延长生存的机制。