Beijing Key Laboratory for Optical Materials and Photonic Devices, Department of Chemistry, Capital Normal University, Beijing 100048, P. R. China.
Laboratory of Biomedical Materials and Key Lab of Biomedical Materials of Natural Macromolecules, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
J Mater Chem B. 2024 Nov 6;12(43):11165-11171. doi: 10.1039/d4tb01650e.
Tumor microenvironment-activatable photosensitizers have gained significant attention for cancer theranostics. Considering the hypoxic environment of solid tumors, activatable phototheranostic agents with type I PDT are desired to obtain improved cancer treatment efficiency. Herein, we report a simple, effective and multifunctional Bodipy photosensitizer for tumor imaging and type I/II photodynamic therapy. The photosensitizer featuring a methylphenylboronic acid pinacol ester group at the -position of Bodipy specifically responds to tumor-abundant HO. Its photophysical properties were characterized using steady-state and time-resolved transient optical spectroscopies. The fluorescence ( = 0.09%) and singlet oxygen efficacy ( = 10.2%) of the Bodipy units were suppressed in the caged dyads but significantly enhanced ( = 0.72%, = 20.3%) upon HO activation. Fluorescence emission spectroscopy and continuous wave electron paramagnetic resonance (EPR) spectroscopy confirmed that the Bodipy photosensitizer generates reactive oxygen species (ROS) via both electron transfer-mediated type I and energy transfer-mediated type II mechanisms. experiments demonstrated rapid internalization into tumor cells, enhanced brightness stimulated by tumor microenvironments, and tumor cell death (phototoxicity, IC = 0.5 μM). fluorescence imaging indicated preferential accumulation of this Bodipy photosensitizer in tumor sites, followed by decaging by tumor-abundant HO, further elevating the signal-to-background ratio (SBR) of imaging. Besides outstanding performance in tumor imaging, a prominent inhibition of tumor growth was observed. Given its simple molecular skeleton, this Bodipy photosensitizer is a competitive candidate for cancer theranostics.
肿瘤微环境激活型光敏剂在癌症治疗学中受到了广泛关注。鉴于实体瘤的缺氧环境，人们希望具有 I 型 PDT 的可激活光热疗试剂能够提高癌症治疗效率。在此，我们报告了一种简单、有效且多功能的 Bodipy 光敏剂，用于肿瘤成像和 I/II 光动力治疗。该光敏剂在 Bodipy 的 -位具有甲基苯硼酸频哪醇酯基团，可特异性响应肿瘤中丰富的 H2O2。我们使用稳态和时间分辨瞬态光学光谱对其光物理性质进行了表征。在笼状二联体中，Bodipy 单元的荧光（φF = 0.09%）和单线态氧效率（φΔ = 10.2%）受到抑制，但在 H2O2 激活后显著增强（φF = 0.72%，φΔ = 20.3%）。荧光发射光谱和连续波电子顺磁共振（EPR）光谱证实，Bodipy 光敏剂通过电子转移介导的 I 型和能量转移介导的 II 型机制产生活性氧物种（ROS）。细胞摄取实验表明，该 Bodipy 光敏剂能够快速进入肿瘤细胞，受肿瘤微环境刺激后荧光强度增强，并导致肿瘤细胞死亡（光毒性，IC = 0.5 μM）。荧光成像表明，该 Bodipy 光敏剂优先在肿瘤部位积聚，随后被肿瘤中丰富的 H2O2 去笼化，进一步提高了成像的信噪比（SBR）。除了在肿瘤成像方面的优异性能外，还观察到肿瘤生长的显著抑制。鉴于其简单的分子骨架，该 Bodipy 光敏剂是癌症治疗学的一种有竞争力的候选药物。
