Lysosome-targeted Aza-BODIPY photosensitizers for anti-cancer photodynamic therapy.

Abstract

Developing effective near-infrared (NIR) photosensitizers (PSs) has been an attractive goal of photodynamic therapy (PDT) for cancer treatment. In this study, we synthesized N, N-diethylaminomethylphenyl-containing Aza-BODIPY photosensitizers and comprehensively investigated their photophysical/photochemical properties, as well as cell-based and animal-based anti-tumor studies. Among them, BDP 1 has strong NIR absorption at 680 nm and higher singlet oxygen yield in PBS which showed favorable pH-activatable and lysosome-targeting ability. BDP 1 could be easily taken up by tumor cells and showed negligible dark activity (IC50 > 50 μM), however strong phototoxicity upon exposure to light irradiation. The acceptable fluorescence emission from BDP 1 allowed convenient in vivo fluorescence imaging for organ distribution studies in mice. After PDT treatment with upon single time PDT treatment at the beginning using relatively low light dose (54 J/ cm2), BDP 1 (2 mg/kg, 0.1 mL) was found to have strong efficacy to inhibit tumor growth and even to ablate off tumor without causing body weight loss. Therefore, pH-activatable and lysosome-targeted PS may become an effective way to develop potent PDT agent.

• Authors: Mei Hu, Xiaochun Dong, Weili Zhao
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 99 Pg. 117583 (Feb 01 2024) ISSN: 1464-3391 [Electronic] England
• PMID: 38198943 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier Ltd. All rights reserved.

Chemical References

• Photosensitizing Agents
• azaBDPBA compound
• Boron Compounds

Topics

• Mice
• Animals
• Photosensitizing Agents (pharmacology, therapeutic use, chemistry)
• Photochemotherapy (methods)
• Boron Compounds (pharmacology, therapeutic use, chemistry)
• Neoplasms (drug therapy)
• Lysosomes