Tissue factor-specific ultra-bright SERRS nanostars for Raman detection of pulmonary micrometastases

Abstract

Here we demonstrate a novel application of ‘surface enhanced resonance Raman scattering nanoparticles’ (SERRS NPs) for imaging breast cancer (BC) lung metastases with much higher precision than currently feasible. The BC lung metastasis mouse model was established by intravenous injection of LM2 cells. SERRS NPs conjugated with ALT-836, an anti-tissue factor (TF) monoclonal antibody, were administered to these mice intravenously and subjected to Raman imaging to visualize the expression of TF both in vivo and ex vivo. Raman imaging indicated marked uptake of αTF-SERRS NPs by the lung metastases (n=4) compared to isotype (n=4) and blocking controls (n=3). Conversely, little uptake of αTF-SERRS NPs was observed in the lungs of healthy mice. Successful detection and delineation of pulmonary micrometastatic lesions as small as 200 μm, corroborated by histology, immunohistochemistry, and bioluminescence imaging (BLI) confirmed the suitability of both TF as a target and αTF-SERRS NPs as an effective contrast agent for imaging breast cancer lung metastases. Further advancements of this technique in the form of Raman endoscopes coupled with ultrabright SERRS NPs developed in this work could lead to minimally invasive detection and resection of lung metastases.

DNA-enabled rational design of fluorescence-Raman bimodal nanoprobes for cancer imaging and therapy

“…Due to these advantages, SERS NP-based imaging methods are gaining substantial momentum and are being successfully utilized to delineate exact tumor margins in various cancers, micrometastases, and even precancerous lesions with very high precision in pre-clinical settings 13–17 . More encouragingly, SERS NPs surface-displaying targeting moieties such as antibodies, aptamers, or targeting peptides (e.g., RGD) were shown to delineate tumors more effectively via active targeting in instances where passive targeting is relatively weak 18–23 . The increased precision of imaging the true microscopic tumor margins could reduce unnecessary resection of surrounding healthy tissue and also facilitate surgeries that are presently not feasible because of the proximity of crucial structures such as nerves or blood vessels.…”

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

“…SERS-based contrast agents for intraoperative imaging have higher TBR and greater photostability than those of fluorophore (ICG). [179,180] Most of researches targeted the malignant brain tumors, [181][182][183] and others concerned liver, [173] breast, [184,185] ovarian, [186] and bladder cancers. Strong enhancement and chemical stability are achieved using a gold or silver cover.…”

Molecular Imaging in Nanotechnology and Theranostics

“…Nanoparticle sequestration by the RES allows for imaging of SLNs [53] and tumors in the liver and spleen [54]. When combined with active targeting via antibodies, peptides, or aptamers SERRS NPs were reported to delineate tumors preoperatively and intraoperatively [55], as well as detecting microscopic tumors and metastatic foci in glioblastoma, ovarian cancer, and lung metastases [56-59, 60 ]. Given their potential significance in tumor imaging and non-toxic composition, the timely translation of SERS NPs into the clinic could represent a fundamental improvement in patient morbidity and mortality.…”