Quaternary Ammonium Salt Based NIR‐II Probes for In Vivo Imaging

Abstract

Traditional luminescent materials including fluorescent probes suffer from notorious aggregation‐caused quenching in aqueous solutions. Although several approaches such as the aggregation‐induced emission effect have been developed, it remains a significant challenge to identify an effective and efficient strategy to resolve this issue. Herein, quaternary ammonium salts Q8PBn and Q8PNap as a novel class of bright near infrared window II (NIR‐II, 1000–1700 nm) probes are designed and synthesized, and the twisted intramolecular charge transfer formation at the excited state can be effectively suppressed for the newly designed probes. Furthermore, Q8PNap complexation with fetal bovine serum (Q8PNap/FBS) significantly increases the quantum yield by ≈32‐fold compared with PEGylated tertiary amine Q8P, and Q8PNap/FBS is successfully used to achieve high spatial and temporal resolution imaging of hind limb vasculature, lymphatic system, and small tumor metastasis, as well as precise NIR‐II imaging‐guided tumor and lymph node surgery in small animal models for the first time.

An IR820 Dye–Protein Complex for Second Near‐Infrared Window and Photoacoustic Imaging

“…In contrast, small‐molecule‐based NIR‐II dyes offer distinct advantages with regard to potential clinical translation. Therefore, the development of organic small‐molecule fluorophores represents an important, newly emerging and dynamic research field in molecular imaging . In particular, organic fluorophores such as CH1055, which is based on a donor–acceptor–donor structure including a benzobisthiadiazole derivative as the acceptor, demonstrate attractive optical properties (NIR‐II emission spectra, good quantum yield, high photostability) and excellent in vivo performance .…”

Improving Quantum Yield of a NIR‐II Dye by Phenylazo Group

“…In toluene, the maximal emission wavelengths of TPB, TPB‐AM, TPB‐BAM, and TPB‐AZO are 928, 969, 946, and 909 nm, respectively. By using commercial dye IR 26 as a reference probe (QY = 0.05%), the QYs of TPB, TPB‐AM, TPB‐BAM, and TPB‐AZO in toluene were measured to be about 13.91%, 0.67%, 9.15%, and 21.59% in 850–1500 nm region, and 4.19%, 0.32%, 3.52%, and 5.30% in 1000–1500 nm region, respectively ( Table 1 and Figure S1, Supporting Information). These results indicate the significant effects of the substituents on the absorption and emission spectra and QY of TPB, and reveal that the amino groups on the donor moieties bathochromically shift the absorption and emission bands of the fluorophore and significantly reduce its QY, while the acylation of the amino groups weakens these variation extents.…”

Monitoring the Real‐Time Circulatory System‐Related Physiological and Pathological Processes In Vivo Using a Multifunctional NIR‐II Probe

“…Although fetal bovine serum (FBS) solution has revealed higher signals than human serum albumin (HSA) in our previous study, HSA is the major plasma protein in human blood which has been widely used as an efficient platform in drug delivery system and is more biocompatible in clinical practice than FBS . Therefore, HSA has a large potential to provide a biocompatible complex with CQ‐T for in vivo imaging.…”

“…Our group synthesized the first NIR‐II organic small‐molecule probe, CH1055‐PEG, with superior biocompatibility and unprecedented renal clearance compared to FDA‐approved probes . Subsequently, various NIR‐II organic small‐molecule probes including Q4, IR‐FGP, IR‐FTAP, IR‐FE, H1, FD‐1080, 5H5, HLZ, ECX, CX, BTC1070, and many others were newly designed by both other groups and us. Nevertheless, the majority of existing NIR‐II organic probes encountered a dilemma because of its dearth in good quantum yield.…”

“…To address this challenge, further modification to CH1055‐PEG led to the development of CH1055‐4T, which demonstrated an optimized quantum yield when sulfonated and exposed to fetal bovine serum (FBS) . Compared to FBS, human serum albumin (HSA) is the major plasma protein in human blood which allows it to be a more efficient platform in clinical drug delivery systems due to its brilliant biocompatibility . Moreover, employing strategies of the interaction between NIR‐II probes and HSA may expedite in vivo excretion kinetics and reduce nonspecific binding.…”