Cancer therapies usually suffer from poor targeting ability and serious side effects. Photoactivatable cancer therapy has the significant advantage of a high spatiotemporal resolution, but most photoactivatable prodrugs require decoration with stoichiometric photocleavable groups, which are only responsive to ultraviolet irradiation and suffer from low reaction efficiency. To tackle these challenges, we herein propose a photoactivation strategy with biogenic riboflavin as the photosensitizer to promote the in situ transformation of noncytotoxic dihydroalkaloid prodrugs dihydrochelerythrine (DHCHE), dihydrosanguinarine (DHSAN), and dihydronitidine (DHNIT) into anticancer alkaloid drugs chelerythrine (CHE), sanguinarine (SAN), and nitidine (NIT), respectively, which can efficiently kill cancer cells and inhibit in vivo tumor growth. Meanwhile, the photoactivatable transformation can be in situ monitored by green-to-red fluorescence conversion, which will contribute to easy controlling of the therapeutic dose. The proposed photoactivatable transformation mechanism was also explored by density functional theory (DFT) calculations. We believe this riboflavin-promoted and imaging-guided photoactivation strategy is promising for precise cancer therapy.

中文翻译：

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核黄素促进原位光活化二氢生物碱前药用于癌症治疗

癌症疗法通常存在靶向能力差和副作用严重的问题。可光激活的癌症疗法具有高时空分辨率的显着优势，但大多数可光激活的前药需要用化学计量的光可裂解基团进行修饰，这些基团仅对紫外线照射有反应并且反应效率低。为了应对这些挑战，我们在此提出了一种以生物核黄素为光敏剂的光活化策略，以促进非细胞毒性二氢生物碱前药二氢白屈菜红碱 (DCHHE)、二氢血根碱 (DHSAN) 和二氢硝苷 (DHNIT) 原位转化为抗癌生物碱药物白屈菜红碱 (CHE) 、血根碱（SAN）和两面针碱（NIT），分别能有效杀灭癌细胞并抑制体内肿瘤生长。同时，光活化转化可以通过绿色到红色荧光转换进行原位监测，这将有助于轻松控制治疗剂量。还通过密度泛函理论 (DFT) 计算探索了所提出的光活化转化机制。我们相信这种核黄素促进和成像引导的光激活策略有望用于精确的癌症治疗。