概述由于时空选择性和固有的非侵入性的优势，癌症光疗，包括光动力疗法（PDT）和光热疗法（PTT），作为一种有前途的癌症治疗方法，近年来引起了人们的广泛关注。尽管这一领域取得了值得称赞的进展，但挑战依然存在。在 PDT 中，染料的局限性表现为较低的系间窜越 (ISC) 效率和氧依赖性光活性，导致性能不令人满意，特别是在缺氧条件下。同样，PTT 的染料光热转换效率 (PCE) 也一直存在不足。此外，次优的光疗功效通常表现出有限的免疫反应。这些因素共同对光疗在肿瘤学中的应用产生了重大限制，导致肿瘤抑制有限、肿瘤复发甚至转移。与依赖复杂系统的外部辅助的策略不同，操纵生物相容性染料中的激发态失活途径提供了一种通用的方法系统地应对这些挑战。我们集团为实现这一目标付出了巨大的努力。在本报告中，我们介绍并讨论了通过基于花青染料调节分子电荷转移来优化激发态能量释放途径的历程，花青染料以其卓越的光物理特性和和谐的生物相容性而闻名。研究首先在七次甲基花青染料的中间位置引入氨基，其中分子内电荷转移（ICT）效应导致斯托克斯位移显着扩大。随后，通过在花青中引入功能性缺电子基团诱导的ICT被发现可以减少电子分布的重叠或缩小分子前沿轨道的能隙。这种修饰导致单线态和三线态之间的能隙减小或内部转换的改善，最终提高原发性和远处肿瘤的光疗功效。此外，随着光辅助电荷转移效应的增强，一些花青中发生光诱导分子内电子转移，导致激发态的电荷完全分离。该过程增强了向基态或三重态的转变，分别通过增加 PCE 或活性氧的产量来改善肿瘤光疗并抑制转移。我们将焦点从分子内相互作用转移到分子间相互作用，成功构建并探索了基于分子间电荷转移的花青。这些染料具有模仿自然光合作用的激发态动力学，可产生自由基并促进不依赖于氧的缺氧肿瘤 PDT。最后，我们概述了通过调节分子电荷转移来优化光疗功效的现有挑战和未来方向。该帐户提供了提高光疗性能的分子水平见解，提供了有价值的观点，并启发了功能染料在其他应用领域的发展。

ConspectusDue to the advantages of spatiotemporal selectivity and inherent noninvasiveness, cancer phototherapy, which includes both photodynamic therapy (PDT) and photothermal therapy (PTT), has garnered significant attention in recent years as a promising cancer treatment. Despite the commendable progress in this field, persistent challenges remain. In PDT, limitations in dyes manifest as low intersystem crossing (ISC) efficiency and oxygen-dependent photoactivity, resulting in unsatisfactory performance, particularly under hypoxic conditions. Similarly, PTT encounters consistent insufficiencies in the photothermal conversion efficiency (PCE) of dyes. Additionally, the suboptimal phototherapeutic efficacy often exhibits a limited immune response. These factors collectively impose significant constraints on phototherapy in oncological applications, leading to limited tumor inhibition, tumor recurrence, and even metastasis.Unlike strategies that rely on external assistance with complicated systems, manipulating excited-state deactivation pathways in biocompatible dyes offers a universal way to systematically address these challenges. Our group has devoted considerable effort to achieving this goal. In this Account, we present and discuss our journey in optimizing excited-state energy-release pathways through regulating molecular charge transfer based on cyanine dyes, which are renowned for their exceptional photophysical properties and harmonious biocompatibility. The investigation begins with the introduction of amino groups in the meso position of a heptamethine cyanine dye, where the intramolecular charge transfer (ICT) effect causes a significant enlargement of the Stokes shift. Subsequently, ICT induced by introducing functional electron-deficient groups in cyanines is found to decrease the overlap of electron distribution or narrow the energy gaps of molecular frontier orbitals. Such modifications result in a reduction of the energy gaps between singlet and triplet states or an improvement in internal conversion, ultimately promoting phototherapy efficacy in both primary and distant tumors. Furthermore, with the intensification of the charge transfer effect aided by light, photoinduced intramolecular electron transfer occurs in some cyanines, leading to complete charge separation in the excited state. This process enhances the transition to the ground or triplet states, improving tumor phototherapy and inhibiting metastasis by increasing the PCE or the yield of reactive oxygen species, respectively. Shifting focus from intramolecular to intermolecular interactions, we successfully constructed and explored cyanines based on intermolecular charge transfer. These dyes, with excited-state dynamics mimicking natural photosynthesis, generate radicals and facilitate oxygen-independent hypoxic tumor PDT. Finally, we outlined the existing challenges and future directions for optimizing phototherapeutic efficacy by regulating molecular charge transfer. This Account provides molecular-level insights into improving phototherapeutic performance, offering valuable perspectives, and inspiring the development of functional dyes in other application fields.