Second near-infrared (NIR-II) photothermal agents (PTAs) have attracted immense attention for cancer theranostics due to their weak interaction with biological tissues, deep tissue penetration, and high maximum permissible exposure, which facilitate excellent imaging-guided tumor therapy. However, the existing NIR-II organic small molecule PTAs predominantly emit in the NIR-II window, and are irradiated by visible light (660 nm) or first near-infrared light (808 nm), hindering efficient deep-tissue photothermal therapy (PTT). Here, a D₂-D₁-A-D₁-D₂ structure-based photothermal agent was developed for enhanced NIR-II-absorbed trimodal-imaging-guided PTT upon 1064 nm irradiation; the developed PTA (BBTD-TP) absorbed long wavelengths (over 1000 nm) via intramolecular charge transfer through enhanced donor-acceptor conjugation. After DSPE-PEG₂₀₀₀ coating, the BBTD-TP nanoparticles (NPs) containing molecular rotors and long alkyl chains exhibited a high photothermal conversion efficiency (37.8%) under 1064 nm laser irradiation, which could be utilized for photoacoustic imaging (PAI) and photothermal imaging (PTI). Furthermore, the BBTD-TP NPs retained their fluorescence emission, facilitating fluorescence imaging (FLI). As a combinatorial theranostic nanoplatform, the multifunctional BBTD-TP nanomachine exhibited excellent tumor-ablation performance under 1064 nm laser irradiation, enabling efficient PAI/PTI/FLI-guided PTT in nude mice with B16F10 cells. Thus, this study reports a highly efficient NIR-II PTA and could guide the future design and development of similar PTAs for efficient theranostics.

第二近红外 (NIR-II) 光热剂 (PTA) 因其与生物组织的弱相互作用、深层组织渗透和高最大允许曝光量而引起了癌症治疗学的极大关注，这有助于实现出色的成像引导肿瘤治疗。然而，现有的NIR-II有机小分子PTAs主要在NIR-II窗口发光，并被可见光（660 nm）或第一近红外光（808 nm）照射，阻碍了有效的深层组织光热疗法（PTT） ). 这里，一个 D ₂ -D ₁ -AD ₁ -D ₂开发了基于结构的光热剂，用于在 1064 nm 照射下增强 NIR-II 吸收的三峰成像引导 PTT；开发的 PTA (BBTD-TP) 通过增强的供体-受体共轭通过分子内电荷转移吸收长波长（超过 1000 nm）。DSPE-PEG _2000之后涂层后，含有分子转子和长烷基链的 BBTD-TP 纳米粒子 (NPs) 在 1064 nm 激光照射下表现出高光热转换效率 (37.8%)，可用于光声成像 (PAI) 和光热成像 (PTI)。此外，BBTD-TP NPs 保留了它们的荧光发射，有利于荧光成像 (FLI)。作为组合治疗诊断纳米平台，多功能 BBTD-TP 纳米机器在 1064 nm 激光照射下表现出优异的肿瘤消融性能，能够在 B16F10 细胞裸鼠中实现高效的 PAI/PTI/FLI 引导 PTT。因此，本研究报告了一种高效的 NIR-II PTA，并可以指导未来类似 PTA 的设计和开发，以实现高效的治疗诊断。