Molecular phenotyping and image-guided surgical treatment of melanoma using spectrally distinct ultrasmall core-shell silica nanoparticles.

Abstract

Accurate detection and quantification of metastases in regional lymph nodes remain a vital prognostic predictor for cancer staging and clinical outcomes. As intratumoral heterogeneity poses a major hurdle to effective treatment planning, more reliable image-guided, cancer-targeted optical multiplexing tools are critically needed in the operative suite. For sentinel lymph node mapping indications, accurately interrogating distinct molecular signatures on cancer cells in vivo with differential levels of sensitivity and specificity remains largely unexplored. To address these challenges and demonstrate sensitivity to detecting micrometastases, we developed batches of spectrally distinct 6-nm near-infrared fluorescent core-shell silica nanoparticles, each batch surface-functionalized with different melanoma targeting ligands. Along with PET imaging, particles accurately detected and molecularly phenotyped cancerous nodes in a spontaneous melanoma miniswine model using image-guided multiplexing tools. Information afforded from these tools offers the potential to not only improve the accuracy of targeted disease removal and patient safety, but to transform surgical decision-making for oncological patients.

• Authors: Feng Chen, Brian Madajewski, Kai Ma, Daniella Karassawa Zanoni, Hilda Stambuk, Melik Z Turker, Sébastien Monette, Li Zhang, Barney Yoo, Peiming Chen, Richard J C Meester, Sander de Jonge, Pablo Montero, Evan Phillips, Thomas P Quinn, Mithat Gönen, Sonia Sequeira, Elisa de Stanchina, Pat Zanzonico, Ulrich Wiesner, Snehal G Patel, Michelle S Bradbury
• Journal: Science advances (Sci Adv) Vol. 5 Issue 12 Pg. eaax5208 (12 2019) ISSN: 2375-2548 [Electronic] United States
• PMID: 31840066 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Chemical References

• Silicon Dioxide

Topics

• Animals
• Cell Line, Tumor
• Lymph Nodes (diagnostic imaging, pathology)
• Lymphatic Metastasis (pathology)
• Melanoma (diagnostic imaging, genetics, surgery)
• Mice
• Multimodal Imaging
• Nanoparticles (chemistry, ultrastructure)
• Optical Imaging
• Particle Size
• Phenotype
• Positron Emission Tomography Computed Tomography
• Sentinel Lymph Node Biopsy
• Silicon Dioxide (chemistry)
• Surgery, Computer-Assisted
• Swine
• Swine, Miniature