Surface plasmon resonance (SPR) and surface-enhanced Raman scattering (SERS) are two key surface plasmon technologies that ultimately enable single-molecule-level chemical and biological sensors. Due to the tremendous progress in solution-based synthesis methods, plasmonic nanoparticles with various complex shapes (e.g., spheres, rods, and prisms) have been widely used for surface plasmon resonance and surface-enhanced Raman scattering sensing. Localized surface plasmon resonance (LSPR) around plasmonic nanoparticles enables very high SERS enhancement and SPR sensitivity.

What are Plasmonic Nanoparticles?

Materials such as nanoparticles, nanorods, and nanotubes that exhibit optical properties at the nanometer scale are called plasmonic nanoparticles. Plasmons can be defined as when a metal nanoparticle interacts with light whose size is smaller than or equal to the wavelength, and the free electrons begin to resonate at a certain frequency, called the plasmon resonance frequency. Plasmon resonance is a material property that depends on the shape, size, composition and environment of the nanoparticle. Another viable option for modifying plasmon resonances is the synthesis of multimetallic nanoparticle composites.

Metal nanoparticles of gold (Au), platinum (Pt), and silver (Ag) exhibit high light absorption and light scattering behaviors. Gold and silver nanoparticles display unique spectral responses due to their specific wavelengths of light that can drive collective oscillations of conducting electrons. At the resonance of these plasmonic nanoparticles, their absorption and scattering intensity can be 40 times higher than that of non-plasmonic particles. The tunability and brightness of these nanoparticles make them useful in molecular tracking, imaging, and detection.

Applications of Plasmonic Nanoparticles

  • In vitro biosensors

Detection of biomolecules at nanomolar concentrations is now common in biological laboratories due to the high specificity of antibodies working in conjunction with a variety of labels, including radioisotopes, enzymes, and phosphorus. Single-antibody or sandwich-based detection methods (i.e., ELISA) have been successfully used in combination with plasmonic nanoparticle-labeled antibodies, particularly in areas where low detection sensitivity is required. Antibodies can be covalently bonded to plasmonic nanoparticles using various methods, such as EDC/NHS chemistry-based amide bonding, maleimide groups, and disulfide bonds.

  • Intracellular detection and ex vivo/in vivo imaging

SERS can provide very rich information about the intracellular environment and organelles. However, a challenging issue in applying SERS to cellular systems is how to successfully inject NPs into living cells and maintain effective and detectable SERS signals. The composition of cells and their ability to take up NPs varies greatly depending on the cell type or tissues from which the cells are obtained. Yashchenok et al. used functionalized colloidal particles to probe the intracellular environment. The designed probes are based on the SERS proximity effect or “hotspot” effect of gold nanoparticles and carbon nanotubes to respond to biomolecules in cells, and both are chosen with both functionality and biocompatibility in mind.

  • Therapeutic applications

The applications of plasmonic nanoparticles are not limited to sensing and imaging but also exhibit excellent performance in photothermal systems. Because cancer cells lack a general blood supply, delivering drugs to tumor cells for testing or treatment is a major problem. To reduce damage to healthy cells, ligands capable of targeting target tumor cells are attached to the surface of the nanoparticles. The El-Sayed group reported the use of gold nanorods (Au NRs) for near-infrared-triggered photothermal therapy of HSC-3 tumor cells. First, antibody-labeled Au NRs were used for selective labeling of tumor cells in vitro. When these Au-NRs serve as photothermal contrast agents attached to the cell membrane, near-infrared laser irradiation causes hyperthermia effect and subsequently induces cell apoptosis.

Accessing Plasmonic NPs

Plasmonic nanoparticles have unique optical and physical properties that enable higher sensitivity for in vitro detection and intracellular or in vivo imaging at the nanoscale. These plasmonic nanomaterials in biology and medicine offer new and exciting approaches. CD Bioparticles offers a series of novel gold nanoparticles, silver nanoparticles, and gold nanostars, as a plasmonic core, for SERS-based lateral flow immunoassay.

Electric field therapy is a non-invasive method of tumor treatment that uses alternating electric fields of specific frequency and intensity to selectively destroy mitosis in cancer cells. Electric field therapy can target proteins that are critical to the cancer cell cycle, leading to mitotic arrest, which can cause apoptosis in cancer cells and activate the patient’s own anti-tumor immune response. Electric field therapy has been approved by the FDA for new diagnostic and recurrent gliomas. Experiments with other local solid tumors are ongoing.

Figure 1. Model for TTFields leading to mitotic disruption.

The principle of electric field therapy can be explained by two basic physical principles: dipole permutation and dielectrophoresis. Simply put: one of the biggest features of tumor cells is uncontrolled cell division. Cell division is closely related to the nanoscale biomolecular behavior during the periodic formation and destruction of microtubule polymers. Microtubule polymers are formed by tubulin dimers with highly polarized properties, and they are very sensitive for the external electric field. An external electric field of appropriate intensity and frequency is generated by a non-contact capacitive electrode placed near the tumor, which can interfere with tumor cell division and ultimately destroy the tumor cells.

The unique principle of electric field therapy gives it a special killing effect on cancer cells: 1. It can treat deep tumors. The electric field therapy is non-uniformly distributed throughout the treatment area, covering the geometry of all treatment sites, and the transducer arrays are not attenuated and can therefore be used to treat tumors located deep. 2. Sustainable treatment. Since the electric field does not have a half-life, the electric field is continuously delivered during the treatment. 3. Precise targeting prevents cancer cell division. The electric field can selectively interfere with the cancer cells in the fast-growth mitotic phase that produce highly charged substances, causing them to enter the cell suicide program death, but have no significant effect on the normal cells of the quiescent and dividing phases. 4. Safe and non-invasive. So far, since electric field therapy has no effect on normal cell division, no related adverse events of electric field treatment have been reported. The main side effect is skin irritation. Prevention strategies include proper shaving, cleaning the scalp and frequent replacement of the electrode patch. When skin problems occur, it is usually possible to change the placement of the patch or using oral antibiotics, or corticosteroids. 5. Therapeutic equipment for electric field therapy. Electric field therapy consists of attaching a patient’s non-invasive transducer array and an extracorporeal generator to deliver an electric field through the skin.

In the development of tumor electric field therapy, test and labeling for changes in tubulin are involved, for example, microtubule-labeled antibodies are used to label microtubules, and changes in microtubule formation in tumor cells before and after electric field treatment are observed. In addition, a mitotic marker (phosphorylated histone 3) is also necessary to reflect the effect of the electric field on mitosis. For the study of the final therapeutic effect, the researchers need tumor cell marker antibodies and cell death marker antibodies (Annexin V) to show the specific killing efficiency of the electric field on cancer cells.

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