A Three-Color Fluorescent Supramolecular Nanoassembly of Phototherapeutics Activable by Two-Photon Excitation with Near-Infrared Light

A supramolecular nanoassembly, of about 30 nm in diameter, that consists of a green-fluorescent, β-cyclodextrin-based, branched polymer co-encapsulating a red-emitting singlet oxygen (1O2) photosensitizer and a nitric oxide (NO) photoreleaser, which comprises a blue fluorescent reporter, is here reported. The system exhibits “five-in-one” photofunctionalities. All components can be simultaneously excited in the phototherapeutic window with two-photons by using near-infrared light at 740 nm and despite their close proximity, behave as independent units. This allows for their in vitro visualization in carcinoma cancer cells, due to their distinct green, red, and blue fluorescence, and for the production of both cytotoxic 1O2 and biofunctional NO.