温和的光热疗法(轻度PTT,42-45°C)提供更高水平的生物安全性。然而,其治疗效果受到热休克反应(HSR)的影响,细胞自我防御机制,这引发了热休克蛋白(HSPs)的过度表达,具有修复受损肿瘤细胞的能力。在这里,这项工作通过结合上转换纳米粒子(UCNPs)制造了一种新型纳米反应器,三氯环己烷e6(Ce6),和葡萄糖氧化酶(GOx)到超薄黑磷纳米片(BPNS)上(表示为GOx-BUC)。这种纳米反应器在808nm激光照射下放大轻度PTT效应,调节HSPs介导的细胞自我防御命运。一方面,用980nm激光照射后,UCNPs可以传递能量激发Ce6,导致ROS爆发的产生,在较深的肿瘤组织中实现对HSPs活性的不加选择的损害。另一方面,GOx可以消耗葡萄糖,从而耗尽ATP能量供应并进一步抑制HSPs表达。因此,GOx-BUC在人类结直肠癌小鼠模型中在温和温度下表现出优异的抗肿瘤功效,导致完全抑制肿瘤,副作用可忽略不计。这个黑磷纳米反应器,具有双轨HSP销毁功能,介绍了在保持高生物安全性的同时提高轻度PTT有效性的新观点。
Mild-temperature photothermal therapy (mild-PTT, 42-45 °C) offers a higher level of biosafety. However, its therapeutic effects are compromised by the heat shock response (HSR), a cellular self-defense mechanism, which triggers the overexpression of heat shock proteins (HSPs) with the capacity of repairing the damaged tumor cells. Herein, this work fabricates a novel nanoreactor by incorporating up-conversion nanoparticles (UCNPs), chlorin e6 (Ce6), and glucose oxidase (GOx) onto the ultrathin black phosphorus nanosheet (BPNS) (denoted as GOx-BUC). This nanoreactor amplifies mild-PTT effects under irradiation with an 808 nm laser, modulating HSPs-mediated cellular self-defense fate. On one hand, upon irradiation with a 980 nm laser, UCNPs can transfer energy to excite Ce6, leading to the generation of ROS burst, which achieves indiscriminate damage to HSPs activity in deeper tumor tissues. On the other hand, GOx can consume glucose, thereby depleting the ATP energy supply and further suppressing HSPs expression. Consequently, GOx-BUC exhibits excellent anti-tumor efficacy under mild temperature in a human colorectal cancer mouse model, resulting in complete tumor inhibition with negligible side effects. This black phosphorous nanoreactor, featuring dual-track HSPs destruction functionality, introduces novel perspectives for enhancing mild-PTT effectiveness while maintaining high biosafety.