Multimodal assessment of SERS nanoparticle biodistribution post ingestion reveals new potential for clinical translation of Raman imaging

Abstract

Despite extensive research and development, new nano-based diagnostic contrast agents have faced major barriers in gaining regulatory approval due to their potential systemic toxicity and prolonged retention in vital organs. Here we use five independent biodistribution techniques to demonstrate that oral ingestion of one such agent, gold-silica Raman nanoparticles, results in complete clearance with no systemic toxicity in living mice. The oral delivery mimics topical administration to the oral cavity and gastrointestinal (GI) tract as an alternative to intravenous injection. Biodistribution and clearance profiles of orally (OR) vs. intravenously (IV) administered Raman nanoparticles were assayed over the course of 48h. Mice given either an IV or oral dose of Raman nanoparticles radiolabeled with approximately 100μCi (3.7MBq) of 64Cu were imaged with dynamic microPET immediately post nanoparticle administration. Static microPET images were also acquired at 2h, 5h, 24h and 48h. Mice were sacrificed post imaging and various analyses were performed on the excised organs to determine nanoparticle localization. The results from microPET imaging, gamma counting, Raman imaging, ICP-MS, and hyperspectral imaging of tissue sections all correlated to reveal no evidence of systemic distribution of Raman nanoparticles after oral administration and complete clearance from the GI tract within 24h. Paired with the unique signals and multiplexing potential of Raman nanoparticles, this approach holds great promise for realizing targeted imaging of tumors and dysplastic tissues within the oral cavity and GI-tract. Moreover, these results suggest a viable path for the first translation of high-sensitivity Raman contrast imaging into clinical practice.

Smart‐Dust‐Nanorice for Enhancement of Endogenous Raman Signal, Contrast in Photoacoustic Imaging, and T2‐Shortening in Magnetic Resonance Imaging

“…The concept of silica coating has shown in the recent past that Raman-labeled gold spheres have got a very low cytotoxicity. [35] A potential long-term decomposition of the ultrafine silica layer, however, will have to be carefully monitored.…”

Multiplexed Optical Imaging of Tumor-Directed Nanoparticles: A Review of Imaging Systems and Approaches

“…Rotational scanning is achieved by attaching a prism 126 or some other motorized component 127 to the tip of the fiber-bundle probe. Note that a topical application approach was used in these studies, which enabled rapid binding of SERS NPs to the cell-surface biomarkers on the lumen of GI tract (in <10 min 113 ) with minimal systemic uptake 129 - 131 ). Using topically applied multiplexed SERS NPs, these endoscopes can quantify multiple biomarkers over large areas of the esophagus or colon, in a time period that is consistent with routine endoscopy procedures, thereby offering the potential for early detection of GI cancers.…”

Iron Oxide Nanoradiomaterials: Combining Nanoscale Properties with Radioisotopes for Enhanced Molecular Imaging

“…This justifies why most of the NM are used in MI experiments. Examples include, but are not limited to, quantum dots [ 1 , 2 ], gold nanoparticles [ 3 , 4 ], upconverting nanophosphors [ 5 , 6 ], liposomes [ 7 , 8 ], dendrimers [ 9 , 10 ], carbon nanotubes [ 11 , 12 ], silica nanoparticles [ 13 , 14 ], and perfluorocarbon nanoparticles [ 15 , 16 ].…”