The existence of residual small‐size tumors after surgery is a major factor contributing to the high recurrence rate of glioblastoma (GBM). Conventional adjuvant therapeutics involving both chemotherapy and radiotherapy usually exhibit unsatisfactory efficacy and severe side effects. Recently, two‐photon photodynamic therapy (TP‐PDT), especially excited by the second near‐infrared (NIR‐II) light, offers an unprecedented opportunity to address this challenge, attributed to its combinational merits of PDT and TP excitation. However, this attempt has not been explored yet. On the other hand, the lack of high‐performance photosensitizers (PSs) also hinders the progress of TP‐PDT on GBM. Based on those, a robust TP‐PS, termed MeTTh, is constructed intendedly through elaborately integrating multiple beneficial design strategies into a single molecule, which simultaneously achieves excellent NIR‐II excitation, large absorption cross‐section, aggregation‐induced NIR‐I emission, and prominent Type I/II reactive oxygen species generation. Aided by nanofabrication, an impressive brain structure imaging depth of 940 µm is realized. Moreover, MeTTh nanoparticles smoothly implement precise and efficient treatment of small‐size GBM in vivo under a 1040 nm femtosecond laser irradiation. This study represents first‐in‐class using TP‐PDT on GBM, offering new insights for the therapy of small‐size tumors in complex and vital tissues.

中文翻译：

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一种 NIR-II 双光子可激发 AIE 光敏剂，用于精确有效地治疗原位小尺寸胶质母细胞瘤


手术后残留的小肿瘤的存在是导致胶质母细胞瘤 （GBM） 高复发率的主要因素。涉及化疗和放疗的常规辅助治疗通常表现出不令人满意的疗效和严重的副作用。最近，双光子光动力疗法 （TP-PDT），特别是被第二种近红外 （NIR-II） 光激发，由于其 PDT 和 TP 激发的组合优点，为应对这一挑战提供了前所未有的机会。然而，这种尝试尚未被探索。另一方面，高性能光敏剂 （PS） 的缺乏也阻碍了 TP-PDT 在 GBM 上的进展。基于这些，通过将多种有益的设计策略精心整合到单个分子中来构建一种强大的 TP-PS，称为 MeTTh，同时实现出色的 NIR-II 激发、大吸收截面、聚集诱导的 NIR-I 发射和突出的 I/II 型活性氧生成。在纳米制造的帮助下，实现了令人印象深刻的 940 μm 脑结构成像深度。此外，MeTTh 纳米颗粒在 1040 nm 飞秒激光照射下在体内顺利实现了对小尺寸 GBM 的精确和高效处理。这项研究代表了在 GBM 上使用 TP-PDT 的同类首创，为治疗复杂和重要组织中的小尺寸肿瘤提供了新的见解。