Extracellular vesicles-based pre-targeting strategy enables multi-modal imaging of orthotopic colon cancer and image-guided surgery

Abstract

Backgroud Colon cancer contributes to high mortality rates as the result of incomplete resection in tumor surgery. Multimodal imaging can provide preoperative evaluation and intraoperative image-guiding. As biocompatible nanocarriers, extracellular vesicles hold great promise for multimodal imaging. In this study, we aim to synthesized an extracellular vesicles-based nanoprobe to visualize colon cancer with positron-emission tomography/computed tomography (PET/CT) and near-infrared fluorescence (NIRF) imaging, and investigated its utility in image-guided surgery of colon cancer in animal models. Results Extracellular vesicles were successfully isolated from adipose-derived stem cells (ADSCs), and their membrane vesicles were observed under TEM. DLS detected that the hydrodynamic diameters of the extracellular vesicles were approximately 140 nm and the zeta potential was − 7.93 ± 0.24 mV. Confocal microscopy showed that extracellular vesicles had a strong binding ability to tumor cells. A click chemistry-based pre-targeting strategy was used to achieve PET imaging in vivo. PET images and the biodistribution results showed that the best pre-targeting time was 20 h, and the best imaging time was 2 h after the injection of 68 Ga-L-NETA-DBCO. The NIRF images showed that the tumor had clear images at all time points after administration of nanoparticles and the Tumor/Muscle ratio peaked at 20 h after injection. Our data also showed that both PET/CT and NIRF imaging clearly visualized the orthotopic colon cancer models, providing preoperative evaluation. Under real-time NIRF imaging, the tumor location and tumor boundary could be clearly observed. Conclusions In brief, this novel nanoprobe may be useful for multi-modal imaging of colon cancer and NIRF image-guided surgery. More importantly, this study provides a new possibility for clinical application of extracellular vesicles as nanocarriers. Graphic Abstract

PET/Fluorescence Imaging: An Overview of the Chemical Strategies to Build Dual Imaging Tools

“…The iterative pretargeting approach has also been investigated with NPs for bimodal PET/fluorescence imaging. Jing et al 172 recently proposed a pretargeting strategy by injecting extracellular vesicles that were first isolated from adipose tissue and modified with lipids bearing Cy5 derivatives or azide functions. Twenty hours after injection of the functionalized vesicles in a HCT116 tumor bearing mice model, the [ 68 Ga]L-NETA-DBCO effector was injected to "bring to light" the vesicles accumulated in the tumor by EPR effect via an azido-DBCO SPAAC reaction.…”

NIR-I Dye-Based Probe: A New Window for Bimodal Tumor Theranostics

“…Comparing different pre-targeting and imaging time points, maximum tumor uptake was obtained at 20 h after the injection of Cy7-EV-N 3 and at 2 h after the injection of 68 Ga-L-NETA-DBCO. The radiation exposure was obviously reduced based on this strategy ( Jing et al, 2021b ).…”

Tumor-Targeting NIRF/MR Dual-Modal Molecular Imaging Probe for Surgery Navigation

“…Multimodality imaging, having attracted wide attention over the past two decades, is an innovative strategy combining the advantages of different imaging modalities and providing molecular and anatomic information about disease sites. − Diverse bimodality imaging probes were designed to diagnose a variety of diseases, especially malignant tumor. For instance, Shi and co-workers exploited a pH/H 2 S dual-stimulus responsive probe to identify the tumor with near-infrared fluorescence/photoacoustic (NIRF/PA) bimodal imaging.…”