Rationally Designed Long-Wavelength Absorbing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy

The utilization of photodynamic therapy
(PDT) for the treatment
of various types of cancer has gained increasing attention over the
last decades. Despite the clinical success of approved photosensitizers
(PSs), their application is sometimes limited due to poor water solubility,
aggregation, photodegradation, and slow clearance from the body. To
overcome these drawbacks, research efforts are devoted toward the
development of metal complexes and especially Ru­(II) polypyridine
complexes based on their attractive photophysical and biological properties.
Despite the recent research developments, the vast majority of complexes
utilize blue or UV-A light to obtain a PDT effect, limiting the penetration
depth inside tissues and, therefore, the possibility to treat deep-seated
or large tumors. To circumvent these drawbacks, we present the first
example of a DFT guided search for efficient PDT PSs with a substantial
spectral red shift toward the biological spectral window. Thanks to
this design, we have unveiled a Ru­(II) polypyridine complex that causes
phototoxicity in the very low micromolar to nanomolar range at clinically
relevant 595 nm, in monolayer cells as well as in 3D multicellular
tumor spheroids.