SERS: Materials, applications, and the future

CONTENTS 1. Introduction 1.1. Fundamental Theory of Surface-Enhanced Raman Scattering 1.2. Optical Properties of SERS Tags 2. Synthesis of SERS Tags 2.1. Noble Metal Nanosubstrates 2.1.1. Single Particle-Based SERS Substrates 2.1.2. Nanoparticle Cluster-Based Substrates 2.2. Raman Reporter Molecules 2.2.1. Selection Principles and Reporter Types 2.2.2. Self-Assembled Monolayer Coverage Strategy 2.3. Surface Coating for Protection 2.3.1. Biomolecule Coating 2.3.2. Polymer Coating 2.3.3. Liposome Coating 2.3.4. Silica Coating 2.4. Attachment of Targeting Molecules 3. Bioanalysis Applications 3.1. Ionic and Molecular Detection 3.2. Pathogen Detection 3.3. Live-Cell Imaging 3.3.1. Cancer Marker Detection 3.3.2. Intercellular Microenvironment Sensing 3.4. Tissue SERS Imaging 3.5. In Vivo SERS Imaging 4. Challenges and Perspectives 4.1. Reproducible Signal of SERS Tags 4.1.1. Precisely Controlled Hot Spots for Nanosubstrates 4.1.2. Calibration of SERS Intensities and Enhancements 4.2. Improving Multiplexing Capability 4.3. Reduced Size for Subcellular Imaging 4.4. Development of Multifunctional Nanoplatforms 4.4.1. Magnetic SERS Dots 4.4.2. Multimodal Imaging Dots 4.4.3. SERS Tag-Based Therapeutic Systems 4.5. Biocompatibility 5. Conclusions and Remarks

SERS Tags: Novel Optical Nanoprobes for Bioanalysis

Photodynamic therapy (PDT) has been applied to treat a wide range of medical conditions, including wet age-related macular degeneration psoriasis, atherosclerosis, viral infection and malignant cancers. However, the tissue penetration limitation of excitation light hinders the widespread clinical use of PDT. To overcome this “Achilles' heel”, deep PDT, a novel type of phototherapy, has been developed for the efficient treatment of deep-seated diseases. Based on the different excitation sources, including near-infrared (NIR) light, X-ray radiation, and internal self-luminescence, a series of deep PDT techniques have been explored to demonstrate the advantages of deep cancer therapy over conventional PDT excited by ultraviolet-visible (UV-Vis) light. In particular, the featured applications of deep PDT, such as organelle-targeted deep PDT, hypoxic deep PDT and deep PDT-involved multimodal synergistic therapy are discussed. Finally, the future development and potential challenges of deep PDT are also elucidated for clinical translation. It is highly expected that deep PDT will be developed as a versatile, depth/oxygen-independent and minimally invasive strategy for treating a variety of malignant tumours at deep locations.

Overcoming the Achilles' heel of photodynamic therapy.

Localized surface plasmon resonance: nanostructures, bioassays and biosensing--a review.

This critical review will present the role of nanoparticles (NPs) in the directions that are vital to the new field of nanomedicine, including imaging and drug delivery. We reflect on the physical properties that make NPs advantageous for in vivo efficacy, and review recent advances in major NP based biomedical applications. Critical questions of transport, uptake, and clearance will be discussed and illustrated through the success and opportunities of NP imaging and therapy on a photodynamic therapy (PDT) based NP system that has been developed in our lab over the past decade (540 references).

The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapy

This article provides an overview of the development and application of plasmonic nanoprobes developed in our laboratory for biosensing and bioimaging. We describe the use of plasmonics surface-enhanced Raman scattering (SERS) gene probes for the detection of diseases using DNA hybridization to target biospecies (HIV gene, breast cancer genes etc.). For molecular imaging, we describe a hyperspectral surface-enhanced Raman imaging (HSERI) system that combines imaging capabilities with SERS detection to identify cellular components using Raman dye-labeled silver nanoparticles in cellular systems The detection of specific target DNA sequences associated with breast cancer using "molecular sentinel" nanoprobes and the use of a plasmonic nanosensor to monitor pH in single cells are presented and discussed.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jbio.200910015

Plasmonic nanoprobes for SERS biosensing and bioimaging.

Products, compositions, systems, and methods for modifying a target structure which mediates or is associated with a biological activity, including treatment of conditions, disorders, or diseases mediated by or associated with a target structure, such as a virus, cell, subcellular structure or extracellular structure. The methods may be performed in situ in a non-invasive manner by placing a nanoparticle having a metallic shell on at least a fraction of a surface in a vicinity of a target structure in a subject and applying an initiation energy to a subject thus producing an effect on or change to the target structure directly or via a modulation agent. The nanoparticle is configured, upon exposure to a first wavelength λ1, to generate a second wavelength λ2 of radiation having a higher energy than the first wavelength λ1. The methods may further be performed by application of an initiation energy to a subject in situ to activate a pharmaceutical agent directly or via an energy modulation agent, optionally in the presence of one or more plasmonics active agents, thus producing an effect on or change to the target structure. Kits containing products or compositions formulated or configured and systems for use in practicing these methods.

Non-invasive energy upconversion methods and systems for in-situ photobiomodulation

In this paper, we describe the development and application of a pH-sensitive plasmonics-active fiber-optic nanoprobe suitable for intracellular bioanalysis in single living human cells using surface-enhanced Raman scattering (SERS) detection. The effectiveness and usefulness of SERS-based fiber-optic nanoprobes are illustrated by measurements of intracellular pH in HMEC-15/hTERT immortalized “normal” human mammary epithelial cells and PC-3 human prostate cancer cells. The results indicate that fiber-optic nanoprobe insertion and interrogation provide a sensitive and selective means to monitor cellular microenvironments at the single cell level.

/pdf/sers-based-plasmonic-nanobiosensing-in-single-living-cells-32gqiev3kc.pdf

SERS-based plasmonic nanobiosensing in single living cells

A system for energy upconversion and/or down conversion and a system for producing a photostimulated reaction in a medium. These systems include 1) a nanoparticle configured, upon exposure to a first wavelength λ 1 of radiation, to generate a second wavelength λ 2 of radiation having a higher energy than the first wavelength λ 1 and 2) a metallic structure disposed in relation to the nanoparticle. A physical characteristic of the metallic structure is set to a value where a surface plasmon resonance in the metallic structure resonates at a frequency which provides a spectral overlap with either the first wavelength λ 1 or the second wavelength λ 2 , or with both λ 1 and λ 2 . The system for producing a photostimulated reaction in a medium includes a receptor disposed in the medium in proximity to the nanoparticle which, upon activation by the second wavelength λ 2 , generates the photostimulated reaction.

Up and down conversion systems for production of emitted light from various energy sources

We report development of a nanoparticle-based, X-ray-activated anticancer "nanodrug" composed of yttrium oxide (Y(2)O(3)) nanoscintillators, a fragment of the HIV-1 TAT peptide, and psoralen. In this formulation, X-ray radiation is absorbed by the Y(2)O(3) nanoscintillators, which then emit UVA light. Absorption of UVA photons by nanoparticle-tethered psoralen has the potential to cross-link adenine and thymine residues in DNA. UVA-induced cross-linking by free psoralen upon activation with UVA light has previously been shown to cause apoptosis in vitro and an immunogenic response in vivo. Studies using the PC-3 human prostate cancer cell line demonstrate that X-ray excitation of these psoralen-functionalized Y(2)O(3) nanoscintillators yields concentration-dependent reductions in cell number when compared to control cultures containing psoralen-free Y(2)O(3) nanoscintillators.

Jonathan P. Scaffidi

Papers

Plasmonic nanoprobes for SERS biosensing and bioimaging.

Non-invasive energy upconversion methods and systems for in-situ photobiomodulation

SERS-based plasmonic nanobiosensing in single living cells

Up and down conversion systems for production of emitted light from various energy sources

Activity of psoralen-functionalized nanoscintillators against cancer cells upon X-ray excitation.