Modified Indulines: From Dyestuffs to In Vivo Theranostic Agents

The efficient, versatile, and straightforward synthesis of the first N-alkyl analogues of induline 3B (8a and 8b) is reported. Thanks to the introduction of lipophilic substituents and their attractive photophysical properties (far-red emission and production of singlet oxygen), phenazinium 8b 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 in vitro and in vivo after illumination (lambda(exc) = 540-560 nm). The molecular structure of 8b 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.

Automated summary

This study reports the efficient synthesis of N-alkyl analogues of induline 3B, with phenazinium 8b showing promising photophysical properties and remarkable abilities for imaging and treating cancer cells at very low concentrations. The molecular structure of 8b is based on a minimalist design, highlighting the emergence of versatile fluorescent probes for targeted photodynamic cancer therapy.