Red-Light-Triggered In Vitro and In Vivo Photocatalytic Cancer Therapy with Polypyridyl Os(II) Photocatalysts

Herein, we have designed, synthesized, and characterized four Os(II) photocatalysts, viz, [Os(phtpy)₂](PF₆)₂ (Os1), [Os(CF₃-phtpy)₂](PF₆)₂ (Os2), [Os(OH-phtpy)₂](PF₆)₂ (Os3), and [Os(quinoline-tpy)₂](PF₆)₂ (Os4). Os1-Os4 exhibited high absorption in the red region, making them suitable candidates for red-light-triggered catalytic anticancer applications. SC-XRD analysis of Os3 and Os4 confirmed the distorted octahedral geometry of the Os^IIN₆ core. Theoretical studies provided insight into the electronic structure and excited-state properties of Os1-Os4. Under red light (633 nm, 27 mW cm^-2), Os1-Os4 exhibited selective NADH oxidation with TOF up to 13.70 h^-1 and efficient ROS generation (Φ_1O2 up to 0.25). As a consequence, Os1-Os4 exhibited pronounced red-light-triggered anticancer activity against MDA-MB-231, MCF-7, and HeLa cells. Moreover, in vivo studies using an orthotopic mouse model revealed that Os4 significantly reduced tumor volume in a dose-dependent manner upon 650 nm laser (90 J cm^-2) exposure by upregulating Bax and downregulating Bcl-2, while it had good in vivo biosafety in the dark.