Ir-organometallic compounds-mediated internal and external dual-phototheranostics for collaborative antitumor therapy.

Cerenkov light-based excitation represents an attractive alternative to conventional external light excitation, aiming to break the penetration limitations of in vivo optical imaging and therapy. However, Cerenkov light's inherent deficiency severely restricts its potential applications in tumor theranostic. Herein, we have seamlessly integrated organometallic compounds with radio-phototheranostics for the first time, achieving significant tumor inhibition and the inaugural instance of a radionuclide(F)-activated NIR photosensitizer with a wavelength exceeding 800 nm through the innovative "internal-external attack" design and "two-in-one" internal energy transfer. In this study, coumarin 6 and IR775 derivatives were connected via iridium atoms to construct dual-function iridium-organometallic compounds (IR-C6Ir), combining internal and external responsive molecules for dual phototherapy and Cerenkov light red-shift fluorescence imaging. IR-C6Ir can be preferably accumulated at mitochondrial at the tumor site, inducing excellent anti-tumor effect with a 92.5 % tumor volume reduction at the lower concentration (0.65 μM) and excitation level (800 μCi of F and 0.5 W/cm of 808 nm laser irradiation). In addition, IR-C6Ir-mediated internal and external phototherapy exhibited the synergistic enhancement effect of "1 + 1>2" and achieved tumor multiplex visualization. The combination of internal phototherapy and external phototherapy motifs in one molecule, provides IR-C6Ir with a novel strategy for high-efficiency and low-toxicity phototherapy.