Modified Indulines: From Dyestuffs to Theranostic Agents.

The efficient, versatile, and straightforward synthesis of the first -alkyl analogues of induline 3B ( and ) is reported. Thanks to the introduction of lipophilic substituents and their attractive photophysical properties (far-red emission and production of singlet oxygen), phenazinium can be used as a theranostic agent and shows, at very low concentrations (100 nM), a remarkable ability to (i) image cells and zebrafish embryos with high quality under both mono- (514 nm) and biphotonic (790 and 810 nm) excitations, (ii) efficiently and quickly penetrate cancer cells rather than healthy fibroblasts, and (iii) induce a total or almost total cancer cell death and after illumination (λ = 540-560 nm). The molecular structure of is based on a triamino-phenazinium core only, with no need for additional components, highlighting the emergence of a minimalistic and versatile class of fluorescent probes for targeted photodynamic cancer therapy.