光热疗法（PTT）是一种有前景的治疗方法，副作用最小，不仅可以直接杀死肿瘤，还可以引起免疫原性细胞死亡（ICD）。然而，大多数实体瘤，包括神经母细胞瘤，富含成纤维细胞，这限制了纳米粒子的渗透和递送。氯沙坦是FDA批准的抗高血压药物，已被证明具有打破过度ECM网络的作用。本研究探讨了介孔铂纳米颗粒（MPNs）与氯沙坦联合在抗高血压药物中的应用及潜在机制。通过建立体外和体内神经母细胞瘤模型，对神经母细胞瘤进行PTT。与未经808 nm激光照射的MPNs组相比，经PTT和氯沙坦预处理的Neuro-2a细胞存活率较低，表面钙网蛋白增加，HMGB1和ATP释放较高。该组还表现出最高的体内抗肿瘤功效，肿瘤抑制率约为80%。同时我们发现实验组小鼠外周血中CD3 T细胞、CD4 T细胞和CD8 T细胞显着高于对照组，CD8 PD-1细胞显着低于MPNs Los组和Los激光组。并且Neuro-2a肿瘤组织中PD-1和α-SMA的表达降低。此外，氯沙坦可以减少MPNs和激光治疗引起的肝功能损伤。这项研究表明，氯沙坦诱导的成纤维细胞消融增加了MPNs对肿瘤的渗透。增强的渗透使 PTT 能够杀死更多的肿瘤细胞并协同激活免疫细胞，从而导致 ICD，表明该策略在体内治疗神经母细胞瘤的巨大前景。© 2024 张等人。

Photothermal therapy (PTT) is a promising therapeutic procedure with minimal side effects, which can not only kill tumor directly but also cause immunogenic cell death (ICD). However, most solid tumors, including neuroblastoma, are abundant in fibroblasts, which limit the penetration and delivery of nanoparticles. Losartan is an antihypertensive drug approved by the FDA, and it has been proved to have the effect of breaking down excessive ECM network.In this study, we investigated the application and potential mechanism of the combination of mesoporous platinum nanoparticles (MPNs) and losartan in the PTT of neuroblastoma by establishing neuroblastoma models in vitro and in vivo.Compared to the MPNs group without 808 nm laser irradiation, Neuro-2a cells pretreated with PTT and losartan showed lower survival rates, increased surface calreticulin, and higher release of HMGB1 and ATP. The group also exhibited the highest anti-tumor efficacy in vivo, with a tumor suppression ratio of approximately 80%. Meanwhile, we found that CD3+ T cells, CD4+ T cells and CD8+ T cells from the peripheral blood of experimental group mice were significantly higher than control groups, and CD8+PD-1+ cells were significantly lower than those in MPNs + Los group and Los + laser group. And the expression of PD-1 and α-SMA in Neuro-2a tumors tissue was reduced. Furthermore, losartan could reduce damage of liver function caused by MPNs and laser treatment.This study demonstrated that losartan-induced fibroblasts ablation increased the penetration of MPNs into tumors. Enhanced penetration allowed PTT to kill more tumor cells and synergistically activate immune cells, leading to ICD, indicating the great promise of the strategy for treating neuroblastoma in vivo.© 2024 Zhang et al.