Development of Methods for Biomedical Diagnostics and Therapy using Plasmonic Nanoplatforms

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2023

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Abstract

Plasmonic nanoplatforms have fundamentally changed the landscape of biomedical sciences, particularly in the fields of early disease detection and treatment. Metallic nanoparticles with unique geometries and compositions such as gold nanostars (GNS) and nanorattles (NR) have allowed for the development of highly sensitive and effective platforms for detecting early disease biomarkers such as RNA without the need for laboratory-based sample amplification tools such as polymerase chain reaction (PCR). Furthermore, these plasmonics-active particles have also enabled novel optical methods for deep tissue tumor detection without the associated energy concerns and technical complexity of traditional imaging methods such as X-Ray computed tomography (CT) or magnetic resonance imaging (MRI). Finally, these particles can also be used for their effective photon to heat conversion capabilities for highly specific treatment of cancer tissue. The body of work described here is a culmination of several applications of plasmonic nanoparticles ranging from biomarker disease detection to deep tumor localization and photothermal treatment.

Recent advances in the of plasmonic nanoplatforms utilizing gold nanoparticles have resulted in many applications for point-of-care (POC) diagnostics. Upon laser excitation, the surface plasmons on the gold nanoparticles strongly oscillate, generating a strong electromagnetic field (EF) in the vicinity of the nanoparticle surface. This EF field enhancement, often referred to as the plasmonic effect, can be utilized to greatly increase the Raman scattering signal of molecules near the particle’s surface. This phenomenon called Surface-Enhanced Raman Scattering (SERS) can then be utilized for highly specific diagnostic and therapeutic applications. Our group has developed numerous biosensors that take advantage of this unique plasmonic property for use in non-invasive and non-amplifying biomarker detection. Due to its strong SERS signal, the ultrabright SERS nanorattles were developed as a unique sandwich hybridization biosensor for nucleic acid detection. We have demonstrated their successful use in detecting unamplified RNA genetic biomarkers of squamous cell carcinoma (SCC) for Head and Neck Cancers (HNCs) in a joint project with our clinical collaborator, Dr. Walter Lee, MD.

Nanoparticle platforms have also allowed for the development of novel optical and spectroscopic detection of deeply seated tumors. The unique spectroscopic fingerprint of SERS spectra on Raman-labelled GNS can be paired with optical techniques that separate the excitation laser source from the detector, which allows for deep tissue interrogation. approach This Surface-Enhanced Spatially Offset Raman Spectroscopy (SESORS) modality has allowed for the detection of GNS in tissue model systems such as through the centimeter-thick bone of a monkey skull. This spatial offset detection mechanism was further developed into a more general system known as Optical Recognition of Constructs using Hyperspectral Imaging and Detection (ORCHID). This system takes advantage of the two-dimensional charge-coupled detection (CCD) system itself as a means of physical separation between the source and detector, and by binning pixels of specific radial distances, a novel and digital-based spatial offset system can be utilized for probing deep tissue layers.

Finally, nanoparticles are utilized for the improved and highly targeted treatment of cancer tissue by taking advantage of the enhanced permeation and retention (EPR) effect in tumors. The photothermal heat treatment with GNS allows for highly specific targeted treatment of tumor, thereby minimizing off-target healthy tissue heating. We have demonstrated this in a brain tumor in a mouse model in a collaborative project with our clinical collaborator Dr. Peter Fecci, MD. We have also developed several simulation models utilizing Monte Carlo Photon propagation as well as analytical thermal diffusion models to demonstrate this effect in tissue containing GNS accumulated in a tumor volume. These simulations were then complemented with experimental studies showing the extent of heat using MRI heat imaging and direct contact thermocouples.

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Odion, Ren Arriola (2023). Development of Methods for Biomedical Diagnostics and Therapy using Plasmonic Nanoplatforms. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/27694.

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