Roshanzadeh Amir, Medeiros Hyllana C D, Herrera Christopher K, Malhado Carson, Tomich Anton W, Fisher Steven P, Lovera Sergio O, Bates Matthew, Lavallo Vincent, Lunt Richard R, Lunt Sophia Y
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, United States.
Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, United States.
Angew Chem Int Ed Engl. 2025 Feb 24;64(9):e202419759. doi: 10.1002/anie.202419759. Epub 2025 Jan 31.
Photodynamic therapy (PDT) has emerged as a promising targeted treatment for cancer. However, current PDT is limited by low tissue penetration, insufficient phototoxicity (toxicity with light irradiation), and undesirable cytotoxicity (toxicity without light irradiation). Here, we report the discovery of cyanine-carborane salts as potent photosensitizers (PSs) that harness the near-infrared (NIR) absorbing [cyanine] with the inertness of [carborane]. The implementation of [cyanine] [carborane] salts dramatically enhance cancer targeting of the PSs and decrease cytotoxicity. We characterize the cellular uptake of the cyanine-carborane PSs, organelle localization, generation of reactive oxygen species (ROS) with the ability to cogenerate multiple ROS species, suppression of pro-metastatic pathways, and activation of apoptotic pathways. We further demonstrate the ability of optimized PSs to eliminate tumors in vivo using an orthotopic mouse model of breast cancer. These newly developed [cyanine] [carborane] salt PSs introduce a potent therapeutic approach against aggressive breast cancer while decreasing side effects.
光动力疗法（PDT）已成为一种很有前景的癌症靶向治疗方法。然而，目前的光动力疗法受到组织穿透性低、光毒性（光照毒性）不足以及不良细胞毒性（无光照射时的毒性）的限制。在此，我们报告了花菁 - 碳硼烷盐作为强效光敏剂（PSs）的发现，其利用了吸收近红外（NIR）的[花菁]以及[碳硼烷]的惰性。[花菁][碳硼烷]盐的应用显著增强了光敏剂的癌症靶向性并降低了细胞毒性。我们对花菁 - 碳硼烷光敏剂的细胞摄取、细胞器定位、产生多种活性氧（ROS）的能力、抑制促转移途径以及激活凋亡途径进行了表征。我们进一步使用乳腺癌原位小鼠模型证明了优化后的光敏剂在体内消除肿瘤的能力。这些新开发的[花菁][碳硼烷]盐光敏剂在减少副作用的同时，为侵袭性乳腺癌引入了一种有效的治疗方法。
