Nonemissive Ruthenium Complexes for Near Infrared-II Photodynamic, Photothermal, Sonodynamic, and Sonothermal Therapy Against Drug-Resistant Cancer

Nine nonemissive Ru(II) complexes have been designed
for synergistic
NIR-II (1064 nm) photodynamic, photothermal, sonodynamic, and sonothermal
therapy targeting cisplatin-resistant nonsmall cell lung cancer. Their
quantum yields of singlet oxygen and superoxide anions are significantly
elevated under low-power NIR-II laser irradiation or ultrasound treatment.
The selected complex RY7 completely eradicated drug-resistant
lung cancer tumors in all tested mice when treated simultaneously
with NIR-II laser and ultrasound at a minimal drug dosage in vivo
and was promptly eliminated from the organism. The application of
a single-molecule sensitizer to achieve synergistic NIR-II photodynamic/photothermal/sonodynamic/sonothermal
therapy may provide important insights into the treatment of deeply
located tumors, tackling tumor hypoxia and addressing the complicated
pharmacological mechanisms underlying drug resistance. The two-photon
absorption quantum chemical calculations presented in this study may
also serve as a powerful tool for the rational design and structure–activity
relationship studies of two-photon photosensitizers and optical materials.