The George Washington Cancer Center, The George Washington University, 800 22nd St NW, Washington, 8th Floor Science and Engineering Hall, Washington, DC, 20052, USA.
The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, 111 Michigan Ave NW, 6th Floor Main Hospital, Washington, DC, 20010, USA.
Small. 2018 May;14(20):e1800678. doi: 10.1002/smll.201800678. Epub 2018 Apr 17.
A thermal "window" of immunogenic cell death (ICD) elicited by nanoparticle-based photothermal therapy (PTT) in an animal model of neuroblastoma is described. In studies using Prussian blue nanoparticles to administer photothermal therapy (PBNP-PTT) to established localized tumors in the neuroblastoma model, it is observed that PBNP-PTT conforms to the "more is better" paradigm, wherein higher doses of PBNP-PTT generates higher cell/local heating and thereby more cell death, and consequently improved animal survival. However, in vitro analysis of the biochemical correlates of ICD (ATP, high-motility group box 1, and calreticulin) elicited by PBNP-PTT demonstrates that PBNP-PTT triggers a thermal window of ICD. ICD markers are highly expressed within an optimal temperature (thermal dose) window of PBNP-PTT (63.3-66.4 °C) as compared with higher (83.0-83.5 °C) and lower PBNP-PTT (50.7-52.7 °C) temperatures, which both yield lower expression. Subsequent vaccination studies in the neuroblastoma model confirm the in vitro findings, wherein PBNP-PTT administered within the optimal temperature window results in long-term survival (33.3% at 100 d) compared with PBNP-PTT administered within the higher (0%) and lower (20%) temperature ranges, and controls (0%). The findings demonstrate a tunable immune response to heat generated by PBNP-PTT, which should be critically engaged in the administration of PTT for maximizing its therapeutic benefits.
描述了一种基于纳米颗粒的光热疗法（PTT）在神经母细胞瘤动物模型中引发的免疫原性细胞死亡（ICD）的热“窗口”。在使用普鲁士蓝纳米颗粒进行光热治疗（PBNP-PTT）以治疗神经母细胞瘤模型中已建立的局部肿瘤的研究中，观察到 PBNP-PTT 符合“越多越好”的模式，其中更高剂量的 PBNP-PTT 会产生更高的细胞/局部加热，从而导致更多的细胞死亡，进而提高动物存活率。然而，对 PBNP-PTT 引发的 ICD 的生化相关性（ATP、高迁移率族蛋白 1 和钙网蛋白）的体外分析表明，PBNP-PTT 触发了 ICD 的热窗口。与更高（83.0-83.5°C）和更低（50.7-52.7°C）的 PBNP-PTT 温度相比，PBNP-PTT 引发的 ICD 标志物在最佳温度（热剂量）窗口内高度表达，而这两种温度都导致表达水平降低。随后在神经母细胞瘤模型中的疫苗接种研究证实了体外研究结果，即在最佳温度窗口内给予 PBNP-PTT 可导致长期存活（100 天 33.3%），而在更高（0%）和更低（20%）温度范围内以及对照组（0%）给予 PBNP-PTT 的情况下则存活时间较短。这些发现表明，PBNP-PTT 产生的热量可引发可调节的免疫反应，在 PTT 的应用中应严格控制这一反应，以最大限度地发挥其治疗益处。
