Gold Nanomaterials at Work in Biomedicine *
Valerio Voliani in Nanomaterials and Neoplasms, 2021
Compared to organic dyes, which have also been explored as photothermal agents for PTT [630, 631], Au nanostructures offer a number of distinctive advantages: (i) higher stability against photobleaching, (ii) better targeting capability due to their nanoscale sizes, and (iii) much greater absorption cross sections and thus higher photothermal conversion efficiency [632, 633]. In addition, Au nanostructures can serve as contrast agents for various imaging techniques, making it possible to achieve imaging-guided therapy. The high photothermal conversion efficiency of Au nanostructures minimizes the required particle dosage for PTT. This makes Au a more attractive choice as a hyperthermia-inducing agent over magnetic nanomaterials, which are also known to induce hyperthermia under an alternating magnetic field, but require a relatively high dose for effective treatment (10–100 mg/mm3 tumor) [634]. It is worth emphasizing that Au nanostructures with strong absorption in the NIR region (including nanorods, nanoshells, nanocages, and nanostars) are particularly well-suited for PTT, owing to the penetration depth of lasers at such wavelengths.
Photodynamic Therapy
Henry W. Lim, Nicholas A. Soter in Clinical Photomedicine, 2018
In addition to interacting with molecular oxygen to produce single oxygen, the excited-state photosensitizer molecule can undergo a side reaction leading to loss of absorbance and photosensitizing ability. This process of photobleaching can modify the reciprocity between photosensitizer level and light, since with irradiation there will be a progressive loss of sensitizer. Photobleaching therefore places a limit on the total amount of phototoxicity (PTmax) that can be produced by a given level of photosensitizer for a given light dose. While this can be a problem, it can also be an advantage. Photosensitizer near the surface of the tissue will absorb light and decrease the illumination at a depth. As photosensitizer near the surface bleaches, more light will penetrate more deeply into the tissue.
Nanoparticle-Based Molecular Imaging in Living Subjects
Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman in Molecular Imaging in Oncology, 2008
Qdots have a number of advantages over conventional fluorophores. Fluorophores are plagued by considerable photobleaching, low photostability and chemical stability, have narrow excitation and relatively broad emissions, low quantum yield, and display an inability to easily tune emission wavelength. Each of these issues is often a critical impediment for applications in living subjects for many reasons beyond the scope of this section. This is the reason for the excitement about qdots in the scientific community—nanoscale qdot beacons solve these problems. Further, the prospect of using a single laser to simultaneously excite an array of qdot colors, each targeted to a different cell surface or intracellular disease marker, to monitor the complex cellular changes because of disease is potentially revolutionary. Nevertheless, autofluorescence and sensitivity remain problems for qdots. Solutions to these may exist in the form of a novel in vivo imaging modality—Raman imaging in living subjects (see sections “Nanoshells” and “Carbon Nanotubes”), which has shown subcutaneous sensitivity down to 8.175 pM (62–64).
Tight junctions: from molecules to gastrointestinal diseases
Published in Tissue Barriers, 2023
Aekkacha Moonwiriyakit, Nutthapoom Pathomthongtaweechai, Peter R. Steinhagen, Papasara Chantawichitwong, Wilasinee Satianrapapong, Pawin Pongkorpsakol
As proteins related to the structure of the cell, the integrity of tight junctions was thought to provide a static, impermeable barrier at the site of apical intercellular space complexes. However, this hypothesis was proven to be almost entirely incorrect. In fact, the concept of tight junction dynamics has a long history of over 30 years.126 In the last decade, fluorescence recovery after photobleaching (FRAP) revealed different mobile characteristics of fluorescent protein-tagged tight junctions during a steady state.127–129 Although claudin-1 stably localized at the tight junction region, ZO-1 and occludin are differentially exchangeable at subcellular levels. Notably, tight junction-to-cytoplasm switching of ZO-1 was found to occur in an energy-dependent manner, which required activity of the actin-binding region (ABR) and MLCK. Indeed, ZO-1 switching could occur via either MLCK-dependent or MLCK-independent mechanisms, which are slow and fast kinetics, respectively.23 Meanwhile, occludin passively diffuses between apical and lateral membrane.23 Therefore, it is widely accepted that tight junction remodeling can spontaneously occur.127 These kinetic behaviors of three representative tight junction proteins refute the theory of tight junctions having a static architecture (Figure 3a).
Selective depletion of polymorphonuclear myeloid derived suppressor cells in tumor beds with near infrared photoimmunotherapy enhances host immune response
Published in OncoImmunology, 2022
Takuya Kato, Hiroshi Fukushima, Aki Furusawa, Ryuhei Okada, Hiroaki Wakiyama, Hideyuki Furumoto, Shuhei Okuyama, Seiichiro Takao, Peter L. Choyke, Hisataka Kobayashi
We confirmed that the optimal time for NIR light irradiation was approximately 1 day after Ly6G-IR700 administration by the biodistribution of Ly6G-IR700 injection (Figure S6). Next, invivo therapeutic effects of Ly6G-targeted NIR-PIT were assessed in the three PMN-MDSC-rich allograft models. The treatment regimen and schema are shown in Figure 3(a). All mice injected with Ly6G-IR700 showed an intense 700 nm fluorescence signal within the tumors, and the signal was attenuated immediately after NIR light irradiation, suggesting the photobleaching of Ly6G-IR700 (Figure 3(b)). In all allograft models, the tumor growth was significantly inhibited in the NIR-PIT group compared with the other two groups (Figure 3(c)). Furthermore, the survival of the NIR-PIT group was also significantly prolonged compared with the other two groups in all allograft models (Figure 3(d)). The efficacy of NIR-PIT against MC38-luc tumor, which contained the least amount of PMN-MDSCs, was also evaluated. Although tumor growth was significantly suppressed, the effect was minimal, and no significant difference in survival was observed (Figure 3(e,f)). Thus, these results demonstrated that Ly6G-targeted NIR-PIT inhibited tumor growth, significantly prolonged survival, and was more effective against PMN-MDSC-rich tumors.
Enabling drug discovery and development through single-cell imaging
Published in Expert Opinion on Drug Discovery, 2019
Andrea K. Pomerantz, Farid Sari-Sarraf, Kerri J. Grove, Liliana Pedro, Patrick J. Rudewicz, John W. Fathman, Thomas Krucker
Single-cell fluorescence microscopy is already routinely employed to provide important mechanistic insights in drug discovery. However, despite advances in microscopy hardware and software for data acquisition and analysis at increasingly higher throughput and spatial resolution over the past decade, single-cell imaging assays still lack a seamless integration between acquisition protocols and analysis pipelines. Typical caveats associated with bulk live-cell fluorescence microscopy can pose even greater problems for single-cell imaging studies. For example, a key concern is the trade-off between time resolution and sample size (number of cells/ROIs imaged) in order to generate enough data to be able to draw meaningful conclusions; for single-cell samples with considerable heterogeneity, it can be challenging to define and classify specific phenotypes in an unbiased manner. Photobleaching and phototoxicity of fluorescent labels during image acquisition can also affect data quality. Additional areas of need in single-cell imaging include improved fluorophores and subcellular markers/stains with reliable conjugation methods, more robust hardware/environmental controls, advanced image analysis tools readily accessible to biologists and chemists, and more facile integration of single-cell microscopy and microfluidics hardware.
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