Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China.
Angew Chem Int Ed Engl. 2021 Mar 8;60(11):6047-6054. doi: 10.1002/anie.202015379. Epub 2021 Feb 3.
Chemodynamic therapy (CDT) involves the catalytic generation of highly toxic hydroxyl radicals ( OH) from hydrogen peroxide (H O ) through metal-ion-mediated Fenton or Fenton-like reactions. Fe is a classical catalyst ion, however, it suffers easy oxidation and systemic side-effects. Therefore, the development of a controllable Fe delivery system is a challenge to maintain its valence state, reduce toxicity, and improve therapeutic efficacy. Reported here is a near-infrared (NIR) light-triggered Fe delivery agent (LET-6) for fluorescence (FL) and photoacoustic (PA) dual-modality imaging guided, photothermal primed CDT. Thermal expansion caused by 808 nm laser irradiation triggers the transformation of LET-6 to expose Fe from its hydrophobic layer, which primes the catalytic breakdown of endogenous H O within the tumor microenvironment, thus generating OH for enhanced CDT. LET-6 shows remarkable therapeutic effects, both in vitro and in vivo, achieving 100 % tumor elimination after just one treatment. This high-performance Fe delivery system provides a sound basis for future synergistic metal-ion-mediated cancer therapy.
化学动力学治疗（CDT）涉及通过金属离子介导的芬顿或类芬顿反应，将过氧化氢（H2O2）催化生成高毒性的羟基自由基（OH）。Fe 是一种经典的催化剂离子，但是它容易被氧化和产生全身副作用。因此，开发一种可控的 Fe 输送系统是一个挑战，以维持其价态、降低毒性并提高治疗效果。本研究报道了一种近红外（NIR）光触发的 Fe 输送剂（LET-6），用于荧光（FL）和光声（PA）双模式成像引导、光热引发的 CDT。808nm 激光照射引起的热膨胀触发 LET-6 的转化，使其从疏水性层中暴露 Fe，从而引发肿瘤微环境中内源性 H2O2 的催化分解，从而生成 OH 以增强 CDT。LET-6 在体外和体内均表现出显著的治疗效果，单次治疗后即可实现 100%的肿瘤消除。这种高性能的 Fe 输送系统为未来协同的金属离子介导的癌症治疗提供了良好的基础。
