Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging

Abstract

With suppressed photon scattering and diminished autofluorescence, in vivo fluorescence imaging in the 1,500- to 1,700-nm range of the near-IR (NIR) spectrum (NIR-IIb window) can afford high clarity and deep tissue penetration. However, there has been a lack of NIR-IIb fluorescent probes with sufficient brightness and aqueous stability. Here, we present a bright fluorescent probe emitting at ∼1,600 nm based on core/shell lead sulfide/cadmium sulfide (CdS) quantum dots (CSQDs) synthesized in organic phase. The CdS shell plays a critical role of protecting the lead sulfide (PbS) core from oxidation and retaining its bright fluorescence through the process of amphiphilic polymer coating and transferring to water needed for imparting aqueous stability and compatibility. The resulting CSQDs with a branched PEG outer layer exhibited a long blood circulation half-life of 7 hours and enabled through-skin, real-time imaging of blood flows in mouse vasculatures at an unprecedented 60 frames per second (fps) speed by detecting ∼1,600-nm fluorescence under 808-nm excitation. It also allowed through-skin in vivo confocal 3D imaging of tumor vasculatures in mice with an imaging depth of ∼1.2 mm. The PEG-CSQDs accumulated in tumor effectively through the enhanced permeation and retention effect, affording a high tumor-to-normal tissue ratio up to ∼32 owing to the bright ∼1,600-nm emission and nearly zero autofluorescence background resulting from a large ∼800-nm Stoke's shift. The aqueous-compatible CSQDs are excreted through the biliary pathway without causing obvious toxicity effects, suggesting a useful class of ∼1,600-nm emitting probes for biomedical research.

Multiplexed NIR‐II Probes for Lymph Node‐Invaded Cancer Detection and Imaging‐Guided Surgery

“…Although the peak emission of donor–acceptor–donor (D‐A‐D) dyes and the tail emission of cyanine dyes can be both used for NIR‐II imaging, the benefit of NIR‐II imaging is better realized in the NIR‐IIb sub‐window (>1500 nm), where light can penetrate nearly all tissues . Imaging in the NIR‐IIb window can minimize photon scattering and simultaneously avoid high absorbance by water, affording high resolution of mouse vasculature at depths of several millimeter in the brain or other tissues . Thus, the challenge for NIR‐II imaging is the limited availability of NIR‐IIb fluorophores with both high brightness and biocompatibility .…”

“…f) Measured tumor accumulation signal over postinjection time points. g) Tail vein injection of PEGylation QDs (injection dose: 3 µm, 100 µL) to afford the second channel to visualize the blood vessels over 1500 nm sub‐window . h) Dual‐color overlay of tumor accumulated IR‐FD and vessel‐indicator QDs.…”

NIR-II fluorescence microscopic imaging of cortical vasculature in non-human primates

“…Although our NIR-II fluorescence wide-field microscopy was capable of realizing real-time brain imaging on rhesus macaques, its spatial resolution and SBR were inevitably influenced by out-of-focus signals (fluorescence signals both above and below the focal plane of objective). To address this challenge, we turned to NIR-II fluorescence confocal microscopy, which offers fine optical sectioning and high SBR, as well as large penetration depth from NIR-II fluorescence bioimaging, as demonstrated by ex vivo and in vivo bioimaging in mice 17,36,44,45 . To achieve this capability in large animals, we custom-designed a NIR-II fluorescence confocal microscopic system, modified from our previous lab-built setup 33,41 .…”

A Biocompatible and Near‐Infrared Liposome for In Vivo Ultrasound‐Switchable Fluorescence Imaging

“…A biocompatible core/shell nanoparticle was introduced by Chen's group and demonstrated the ability of fluorescence imaging at 3.2 cm deep porcine muscle tissue via a 980 excitation light . Additionally, in vivo high‐resolution fluorescence imaging was accomplished by using quantum dots, which was in the near‐infrared (NIR)‐IIb window and achieved blood vessel imaging in a mouse . Recently, a 6 cm deep tissue fluorescence imaging was accomplished using an NIR‐II fluorophore and the DOLPHIN imaging system with an excitation light less than 0.5 W cm −2 .…”