Molecular Cancer Imaging in the Second Near‐Infrared Window Using a Renal‐Excreted NIR‐II Fluorophore‐Peptide Probe

Abstract

In vivo molecular imaging of tumors targeting a specific cancer cell marker is a promising strategy for cancer diagnosis and imaging guided surgery and therapy. While targeted imaging often relies on antibody-modified probes, peptides can afford targeting probes with small sizes, high penetrating ability, and rapid excretion. Recently, in vivo fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) shows promise in reaching sub-centimeter depth with microscale resolution. Here, a novel peptide (named CP) conjugated NIR-II fluorescent probe is reported for molecular tumor imaging targeting a tumor stem cell biomarker CD133. The click chemistry derived peptide-dye (CP-IRT dye) probe afforded efficient in vivo tumor targeting in mice with a high tumor-to-normal tissue signal ratio (T/NT > 8). Importantly, the CP-IRT probes are rapidly renal excreted (≈87% excretion within 6 h), in stark contrast to accumulation in the liver for typical antibody-dye probes. Further, with NIR-II emitting CP-IRT probes, urethra of mice can be imaged fluorescently for the first time noninvasively through intact tissue. The NIR-II fluorescent, CD133 targeting imaging probes are potentially useful for human use in the clinic for cancer diagnosis and therapy.

Targeting Peptide‐Based Probes for Molecular Imaging and Diagnosis

“…Additionally, imaging‐guided surgery was achieved . On this basis, a new peptide‐conjugated NIR‐II fluorescent probe reached its in vivo signal peak in only 2 h and was rapidly renal excreted (≈87% excretion within 6 h) in stark contrast to the accumulation of antibody‐based probes in the liver (Figure B) . The advantages of real‐time detection, sensitivity, rapidness, and blood clearance are demonstrated in this example.…”

“…Compared with the protein‐labeled dye, the peptide‐labeled dye could be excreted from the urinary system (bottom middle) because of the different size (bottom right). Reproduced with permission . Copyright 2018, Wiley‐VCH.…”

“…The CSC marker CD133 (prominin‐1) is especially noticeable. New peptide ligands with nanomolar affinity for CD133 have been discovered and could be used for in vivo noninvasive imaging of early‐stage tumors . Finally, researchers have begun to focus on several immunotherapy targets.…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…[94] Peptides are among the most popular targeting ligands due to their rapid clearance, high affinities, and specificities for their targets. [38,39,96] Wang et al reported an in vivo assembling downconversion NP (DCNP) modified with DNA (L 1 ) and follicle-stimulating hormone (FSH β ) peptide (called DCNP-L 1 -FSH β ). [38,39,96] Wang et al reported an in vivo assembling downconversion NP (DCNP) modified with DNA (L 1 ) and follicle-stimulating hormone (FSH β ) peptide (called DCNP-L 1 -FSH β ).…”

“…[38] After two-staged sequential intravenous injections, DCNP-L 1 -FSH β achieved stable retention in tumors and superior T/NT ratio from 20 to 26 h PI, with an ≈6 h optimal surgical time window (Figure 3b-e). [96] CP targeted a tumor stem cell biomarker CD133 to facilitate tumor detection by molecular imaging. Dai's team developed an NIR-II fluorescence probe (CP-IRT) with improved T/NT signal ratio by conjugating a novel peptide CP to a fluorophore IRT based on donor-accepter-donor (D-A-D) structure.…”