Novel HER2-Targeted Peptide for NIR-II Imaging of Tumor

Abstract

Molecular targets serve a crucial role in drug development. Herein, we discovered a novel peptide that can specifically target the human epidermal growth factor receptor 2 (HER2) and thus named it Herceptide. In our study, Herceptide was conjugated to the near-infrared fluorescent dye indocyanine green (ICG) to obtain a probe, ICG-Herceptide. Importantly, specific binding to HER2 was revealed by molecular docking, surface plasmon resonance analysis, and competition assays. The probe showed high binding affinity (K D = 1.03 nM) and fast binding property (k on = 0.44 min −1 ). In vivo near-infrared window two (NIR-II, 1000−1700 nm) imaging in HER2-overexpressed SKOV3 tumor-bearing mice demonstrated a high tumor-to-normal tissue signal ratio (T/N = 7.3) at 8 h postinjection. In the blocking study, ICG-Herceptide coinjected with Herceptide only showed a weak tumor signal. In other HER2 high-expression tumors, such as non-small-cell lung cancer A549 and gastric cancer MKN45, the tumor-to-normal tissue signal ratios (T/N) were 4.1 and 4.7, respectively. In contrast, HER2 low-expression tumor MDAMB231 shows no imaging contrast between the tumor and normal tissues. Furthermore, tumor resection was successfully performed under the guidance of the ICG-Herceptide-based NIR-II imaging in subcutaneous SKOV3 mice models. The biocompatibility study indicated that the probe had no observable toxicity to cells and tissues. Overall, these results demonstrate that ICG-Herceptide is a promising optical probe for the diagnosis and localization of HER2-overexpressing tumors. Moreover, Herceptide is a novel HER2targeting peptide and can be further used for developing theranostic agents.

Development of a Novel HER2-Targeted Peptide Probe for Dual-Modal Imaging of Tumors

“…The novel HER2-targeted peptide Herceptide (RSLWSDFYASASRGP) has 15 amino acids and was reported in our recent study. 35 Functional fragments were searched by reducing amino acids in the sequence, resulting in 11 derivative peptides. We screened all the derivative peptides through computer simulation molecular docking, and the short peptide (RSLWSDFY) had the highest score (−11.3811) and was named ZC01 (Table S1).…”

“…The novel HER2-targeted peptide Herceptide (RSLWSDFYASASRGP) has 15 amino acids and was reported in our recent study . Functional fragments were searched by reducing amino acids in the sequence, resulting in 11 derivative peptides.…”

“…Our recent study identified Herceptide (RSLWSDFYA-SASRGP) as a novel targeting peptide for HER2. 35 In this study, we used molecular docking technology to screen out the core sequence of Herceptide (RSLWSDFY) named the ZC01 peptide. Another HER2-targeted peptide KSPNPRF (abbre-viated as KSP) reported 33 was also selected in this study for constructing a dual-modal probe.…”

“…Our recent study identified Herceptide (RSLWSDFYASASRGP) as a novel targeting peptide for HER2 . In this study, we used molecular docking technology to screen out the core sequence of Herceptide (RSLWSDFY) named the ZC01 peptide.…”

Harnessing the power of molecular imaging for drug discovery and development

“…Molecular imaging is a new generation of imaging modality that employs contrast agents to enable in vivo qualitative and quantitative analysis and detection of physiological processes at the molecular level, thus providing information unavailable through traditional imaging modalities [1], such as optical imaging [2–4], ultrasound imaging [5, 6], magnetic resonance imaging (MRI) [7–9], single‐photon emission computed tomography (SPECT) [10], and positron emission tomography (PET) [11–13]. Molecular optical imaging based on phenomena such as fluorescence, Raman scattering, chemiluminescence, and bioluminescence is widely used for disease diagnosis, drug development, and pathological analysis owing to its high sensitivity, high contrast ratio, high resolution, and high imaging speed [14, 15].…”