Redox-Inactive Terpyridine Zn(II)-Azide Complexes for Photodynamic and Photoactivatable Chemotherapy

Area of Science:

• Materials Science
• Chemistry
• Biomedical Engineering

Background:

• Developing metal complexes for combined photodynamic therapy (PDT) and photoactivatable chemotherapy (PACT) is challenging.
• Terpyridine zinc(II)-azide complexes offer potential for novel phototherapeutic strategies.

Purpose of the Study:

• To design and evaluate a terpyridine zinc(II)-azide complex for synergistic PDT and PACT.
• To investigate the mechanism of action and efficacy of the lead complex Tpatpy@ZnN3.

Main Methods:

• Synthesis of terpyridine zinc(II)-azide complexes.
• Evaluation of Tpatpy@ZnN3 for type I and type II PDT, and photorelease of azidyl radicals.
• Assessment of reactive oxygen and nitrogen species generation upon blue light activation (456 nm).
• Testing efficacy in 2D cancer cells and 3D multicellular tumor spheroids.

Main Results:

• Tpatpy@ZnN3 exhibits both type I and type II PDT, releasing azidyl radicals.
• Blue light activation generates singlet oxygen, hydroxyl radical, and azidyl radical, inducing oxidative stress.
• The complex effectively eliminates 2D cancer cells and 3D tumor spheroids.
• Tpatpy@ZnN3 demonstrates biocompatibility, cost-effectiveness, redox inactivity, and negligible dark toxicity.

Conclusions:

• Tpatpy@ZnN3 shows significant potential for synergistic phototherapy with precise spatial and temporal control.
• This zinc(II) complex offers a promising platform for developing advanced photoactivatable agents for cancer therapy.