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

Abstract

Activatable second near‐infrared window (NIR‐II; 1.0–1.7 µm) 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.

Rational design of a multifunctional molecular dye for dual-modal NIR-II/photoacoustic imaging and photothermal therapy

“…18,19 Over the past several years, uorescence based imaging in the second near-infrared channel (NIR-II, 1000-1700 nm) has gained attention for its prominent merits and surpasses the conventional visible/NIR-I channels (700-900 nm) in terms of lower tissue scattering and minimal auto-uorescence, thus leading to signicant advances in imaging qualities including image depth and spatiotemporal resolution. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] More recently, based on a benzobisthiadiazole (BBTD) acceptor, a series of small molecular dyes with a donor-acceptor-donor (D-A-D) architecture have been developed. The reduced energy gap between the hybridized highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) levels in these molecular systems shied the uorescence emission spectrum from the NIR-I region to the NIR-II channel.…”

Semiconducting Polymer Dots with Dual‐Enhanced NIR‐IIa Fluorescence for Through‐Skull Mouse‐Brain Imaging

“…[3] Accordingly,N IR-II fluorescent probes have attracted considerable attention in the past few years. [4] Fori nstance,D ai and co-workers developed as eries of NIR-II fluorescent probes and demonstrated the superior performance of in vivo NIR-II imaging. [5] Cheng et al synthesized ad iketopyrrolopyrrole polymer exhibiting NIR-II fluorescence,a nd the corresponding nanoparticles were capable of assisting accurate image-guided tumor surgery.…”

Recent Advances on Activatable NIR‐II Fluorescence Probes for Biomedical Imaging

“…In 2019, Fan's group first reported a generic and novel design strategy with bio-erasable intermolecular donor-acceptor interaction to construct a ClO − -responsive NIR-II fluorescence semiconducting nanoprobe (Figure 7a-c). [77] The nanoprobe SPNP25 is achieved through blending a ClO − -responsive nonfullerene acceptor 3,9-bis(2-methylene- ( (Figure 7d-f). [78] In this system, excitation wavelength is used at 808 nm, i.e., in the absorption overlapping region, the NIR-II fluorescence of DCNPs is very weak because of the energy filtration by strong absorbance of Cy7.5 at 808 nm under the DCNPs.…”

“…The ratio of NIR-II fluorescence probe was successfully used to detect drug APAP-induced hepatotoxicity in vivo. [77] Copyright 2018, Wiley-VCH. d-f) Reproduced with permission.…”