2025-02-10 カリフォルニア大学リバーサイド校 (UCR)
<関連情報>
- https://news.ucr.edu/articles/2025/02/10/breast-cancer-treatment-advances-light-activated-smart-bomb
- https://onlinelibrary.wiley.com/doi/10.1002/anie.202419759
次世代光増感剤: 転移性癌の優れた光線力学的治療のためのシアニン-カルボラン塩 Next-Generation Photosensitizers: Cyanine-Carborane Salts for Superior Photodynamic Therapy of Metastatic Cancer
Amir Roshanzadeh, Dr. Hyllana C. D. Medeiros, Dr. Christopher K. Herrera, Carson Malhado, Anton W. Tomich, Steven P. Fisher, Sergio O. Lovera, Dr. Matthew Bates …
Angewandte Chemie International Edition Published: 22 January 2025
DOI:https://doi.org/10.1002/anie.202419759
Graphical Abstract
We report a multifaceted assessment of novel cyanine-carborane salts as potent photosensitizers for photodynamic therapy (PDT). These compounds exhibit efficient tumor targeting through uptake by organic anion-transporting polypeptides (OATP). Upon near-infrared (NIR) light irradiation, cyanine-carborane salts generate reactive oxygen species (ROS), triggering apoptosis and significantly suppressing tumor cell proliferation and migration. In vivo studies demonstrate anti-tumor activity with minimal systemic toxicity, highlighting their potential as next-generation PDT therapeutics.
Abstract
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.
