Department Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China.
School of Sino-German Intelligent Manufacturing, Shenzhen Institute of Technology, Shenzhen, 518116, China.
Angew Chem Int Ed Engl. 2024 Oct 21;63(43):e202408064. doi: 10.1002/anie.202408064. Epub 2024 Jul 30.
Tumor-specific activatable long-wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (Φ O) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH-activatable cyanine-based LW PSs (LET-R, R = H, Cl, Br, I), among which the activated LET-I exhibits strong light absorption at 808 nm and a remarkable 3.2-fold enhancement in Φ O compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual-modal imaging-escorted complete photodynamic eradication of tumors by the folic acid (FA)-modified LET-I probe (LET-I-FA), under the ultralow 808 nm laser power density (0.2 W cm) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT.
肿瘤特异性激活型长波长（LW）光敏剂（PS）有望克服传统光动力疗法（PDT）的局限性，例如全身光毒性和浅层组织穿透性。然而，它们的 LW 光吸收不足和单线态氧量子产率（ΦO）通常需要高激光功率密度来产生热能并协同增强 PDT。强烈的光热辐射会引起急性疼痛，显著降低患者的依从性，并阻碍 LW-PDT 的更广泛临床应用。通过激子动力学剖析策略，我们开发了一系列基于花菁的 pH 激活型 LW PS（LET-R，R = H、Cl、Br、I），其中激活的 LET-I 在 808nm 处具有很强的光吸收，并且与吲哚菁绿相比，ΦO 显著提高了 3.2 倍。瞬态光谱分析和理论计算证实了其显著促进的系间窜越和同时增强的 LW 荧光发射特性。这些特性使激活型荧光和光声双模成像能够在超低 808nm 激光功率密度（0.2W/cm）下，通过叶酸（FA）修饰的 LET-I 探针（LET-I-FA）实现肿瘤的完全光动力清除，而无需光热能量协同作用。这项研究提出了一种剖析激子动力学的新策略，用于筛选可用于可追踪 PDT 的激活型 LW PS。
