Department of General Dentistry II, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No.22, Zhongguancun South Avenue Haidian District, Beijing, 100081, P. R. China.
State Key Laboratory of Organic-Inorganic Composites, Key Lab of Biomedical Materials of Natural Macromolecules, Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, 15 North Third Ring Road, Beijing, 100029, P. R. China.
Adv Healthc Mater. 2024 Nov;13(28):e2401981. doi: 10.1002/adhm.202401981. Epub 2024 Jul 28.
Conventional phototherapeutic agents are typically used in either photodynamic therapy (PDT) or photothermal therapy (PTT). However, efficacy is often hindered by hypoxia and elevated levels of heat shock proteins in the tumor microenvironment (TME). To address these limitations, a formylated, near-infrared (NIR)-absorbing and heavy-atom-free Aza-BODIPY dye is presented that exhibits both type-I and type-II PDT actions with a high yield of reactive oxygen species (ROS) and manifests efficient photothermal conversion by precise adjustments to the conjugate structure and electron distribution, leading to a large amount of ROS production even under severe hypoxia. To improve biosafety and water solubility, the dye with an amphiphilic triblock copolymer (Pluronic F-127), yielding BDP-6@F127 nanoparticles (NPs) is coated. Furthermore, inspired by the fact that phototherapy triggers the release of tumor-associated antigens, a strategy that leverages potential immune activation by combining PDT/PTT with immune checkpoint blockade (ICB) therapy to amplify the systemic immune response and achieve the much-desired abscopal effect is developed. In conclusion, this study presents a promising molecular design strategy that integrates multimodal therapeutics for a precise and effective approach to cancer therapy.
传统的光疗剂通常用于光动力疗法（PDT）或光热疗法（PTT）。然而，疗效常常受到肿瘤微环境（TME）中缺氧和热休克蛋白水平升高的阻碍。为了解决这些限制，提出了一种甲酰化的近红外（NIR）吸收且不含重原子的 Aza-BODIPY 染料，它具有高活性氧（ROS）生成的 I 型和 II 型 PDT 作用，并通过对共轭结构和电子分布的精确调整来实现有效的光热转换，即使在严重缺氧的情况下也能产生大量的 ROS。为了提高生物安全性和水溶性，用两亲性三嵌段共聚物（Pluronic F-127）对染料进行了包覆，得到了 BDP-6@F127 纳米颗粒（NPs）。此外，受光疗会引发肿瘤相关抗原释放这一事实的启发，提出了一种策略，即通过将 PDT/PTT 与免疫检查点阻断（ICB）治疗相结合，利用潜在的免疫激活来放大系统免疫反应，实现理想的远隔效应。总之，本研究提出了一种有前途的分子设计策略，将多种治疗方式集成在一起，为癌症治疗提供了一种精确有效的方法。
