Photocatalytic glucose-appended bio-compatible Ir(III) anticancer complexes

Area of Science:

• Organometallic Chemistry
• Photocatalysis
• Cancer Therapy

Background:

• Development of novel photocatalysts for biological applications is crucial.
• Iridium(III) complexes offer unique photophysical properties.
• Targeted cancer therapy requires biocompatible and selective agents.

Purpose of the Study:

• To design and synthesize glucose-appended iridium(III) photocatalysts.
• To investigate their catalytic activity in aqueous solution.
• To evaluate their photocytotoxicity against cancer cells and spheroids.

Main Methods:

• Synthesis of rationally-designed glucose-appended Ir(III) complexes ([Ir(N,C)2(N,N-Glc)]+).
• Visible light-induced catalytic NAD(P)H oxidation assays in aqueous media.
• In vitro evaluation of photocytotoxicity in cancer cell lines and multicellular spheroids, including lysosome and mitochondria targeting.

Main Results:

• The synthesized complexes (Ir1-Ir3) exhibited visible light-induced catalytic NAD(P)H oxidation.
• The biocompatible complex Ir3 demonstrated potent necro-apoptotic photocytotoxicity.
• Ir3 selectively targeted lysosomes and mitochondria in cancer cells.
• Ir3 showed significant efficacy against various cancer cell lines and multicellular spheroids.
• Ir3 exhibited minimal dark toxicity, ensuring a favorable safety profile.

Conclusions:

• Glucose-appended Ir(III) complexes are effective visible-light photocatalysts for NAD(P)H oxidation.
• The biocompatible complex Ir3 shows promise as a targeted phototherapeutic agent for cancer.
• Ir3's ability to target lysosomes and mitochondria, coupled with its dark non-toxicity, highlights its potential for clinical translation.