Bio-Erasable Intermolecular Donor-Acceptor Interaction of Organic Semiconducting Nanoprobes for Activatable NIR-II Fluorescence Imaging

Activatable second near-infrared window (NIR-II; 1.0-1.7 mu m) fluorescence probes that uncage deep-tissue penetrating fluorescence by disease-related biomarker stimuli hold great promise for detecting diseases with a poor understanding of the pathology at the molecular level with unprecedented resolution. However, currently, very few activatable NIR-II fluorescence probes are reported mainly due to the lack of a simple yet general design strategy. Herein, a new and fairly generic design strategy using a bio-erasable intermolecular donor-acceptor interaction to construct activatable NIR-II fluorescence probes is reported. An organic semiconducting nanoprobe (SPNP) is constructed through blending a biomarker-sensitive organic semiconducting non-fullerene acceptor (3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-cyclopentane-1,3-dione-[c]thiophen))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b'] dithiophene) (ITTC) (one of electric acceptors in organic solar cells) with a biomarker-inert semiconducting polymer donor 5-(4,8-bis((2-ethylhexyl)oxy)-6-methylbenzo[1,2-b:4,5-b']difuran-2-yl)-10-methylnaphtho[1,2-c:5,6-c']bis([1,2,5]thiadiazole) (PDF) in an amphiphilic-polymer-coated single nanoparticle to suppress NIR-II fluorescence of the donor via a intermolecular donor-acceptor interaction. The acceptor ITTC is found to be specifically degraded by hypochlorite (an important biomarker) to erase its acceptor property, thus erasing the intermolecular donor-acceptor interaction and uncaging NIR-II fluorescence. Consequently, SPNP exhibits a 17.5-fold higher fluorescence brightness in the hypochlorite-abnormal inflammation in vivo than in normal tissues. Our bio-erasable intermolecular donor-acceptor interaction strategy provides simple yet general guidelines to design various biomarker-activatable NIR-II fluorescence probes.