Effect of a sensing charge mutation on the deactivation of KV7.2 channels.

Potassium-selective, voltage-gated channels of the KV7 family are critical regulators of electrical excitability in many cell types. Removing the outermost putative sensing charge (R198) of the human KV7.2 shifts its activation voltage dependence toward more negative potentials. This suggests that removing a charge "at the top" of the fourth (S4) segment of the voltage-sensing domain facilitates activation. Here, we hypothesized that restoring that charge would bring back the activation to its normal voltage range. We introduced the mutation R198H in KV7.2 with the idea that titrating the introduced histidine with protons would reinstate the sensing charge. As predicted, the mutant's activation voltage dependence changed as a function of the external pH (pHEXT) while modest changes in the activation voltage dependence were observed with the wild-type (WT) channel. On the other hand, the deactivation kinetics of the R198H mutant was remarkably sensitive to pHEXT changes, readily deactivating at pHEXT 6, while becoming slower to deactivate at pHEXT 8. In contrast, the KV7.2 WT displayed modest changes in the deactivation kinetics as a function of pHEXT. This suggested that the charge of residue 198 was critical for deactivation. However, in a surprising turn, the mutant R198Q-a non-titratable mutation-also displayed a high pHEXT sensitivity activity. We thus concluded that rather than the charge at position 198, the protonation status of the channel's extracellular face modulates the open channel stabilization and that the charge of residue 198 is required for the voltage sensor to effectively deactivate the channel, overcoming the stabilizing effect of high pHEXT.

Gold nanoparticles-based photothermal therapy for breast cancer.

AuNPs-mediated photothermal therapy (PTT) is gaining popularity in both laboratory research and medical applications. It has proven clear advantages in breast cancer therapy over conventional thermal ablation because of its easily-tuned features of irradiation light with inside hyperthermia ability. Notwithstanding this significant progress, the therapeutic potential of AuNPs-mediated PTT in cancer treatments is still impeded by several challenges, including inherent non-specificity, low photothermal conversion effectiveness, and the limitation of excitation light tissue penetration. Given the rapid progress of AuNPs-mediated PTT, we present a comprehensive overview of significant breakthroughs in the recent advancements of AuNPs for PTT, focusing on breast cancer cells. With the improvement of chemical synthesis technology, AuNPs of various sizes and shapes with desired properties can be synthesized, allowing breast cancer targeting and treatment. In this study, we summarized the different sizes and features of four major types of AuNPs in this review: Au nanospheres, Au nanocages, Au nanoshells, and Au nanorods, and explored their benefits and drawbacks in PTT. We also discussed the diagnostic, bioconjugation, targeting, and cellular uptake of AuNPs, which could improve the performance of AuNP-based PTT. Besides that, potential challenges and future developments of AuNP-mediated PTT for clinical applications are discussed. AuNP-mediated PTT is expected to become a highly promising avenue in cancer treatment in the near future.

Monodisperse Gold Nanoparticles: A Review on Synthesis and Their Application in Modern Medicine.

Gold nanoparticles (AuNPs) are becoming increasingly popular as drug carriers due to their unique properties such as size tenability, multivalency, low toxicity and biocompatibility. AuNPs have physical features that distinguish them from bulk materials, small molecules and other nanoscale particles. Their unique combination of characteristics is just now being fully realized in various biomedical applications. In this review, we focus on the research accomplishments and new opportunities in this field, and we describe the rising developments in the use of monodisperse AuNPs for diagnostic and therapeutic applications. This study addresses the key principles and the most recent published data, focusing on monodisperse AuNP synthesis, surface modifications, and future theranostic applications. Moving forward, we also consider the possible development of functionalized monodisperse AuNPs for theranostic applications based on these efforts. We anticipate that as research advances, flexible AuNPs will become a crucial platform for medical applications.

Upconversion lanthanide nanomaterials: basics introduction, synthesis approaches, mechanism and application in photodetector and photovoltaic devices.

Upconversion (UC) of lanthanide-doped nanostructure has the unique ability to convert low energy infrared (IR) light to high energy photons, which has significant potential for energy conversion applications. This review concisely discusses the basic concepts and fundamental theories of lanthanide nanostructures, synthesis techniques, and enhancement methods of upconversion for photovoltaic and for near-infrared (NIR) photodetector (PD) application. In addition, a few examples of lanthanide-doped nanostructures with improved performance were discussed, with particular emphasis on upconversion emission enhancement using coupling plasmon. The use of UC materials has been shown to significantly improve the NIR light-harvesting properties of photovoltaic devices and photocatalytic materials. However, the inefficiency of UC emission also prompted the need for additional modification of the optical properties of UC material. This improvement entailed the proper selection of the host matrix and optimization of the sensitizer and activator concentrations, followed by subjecting the UC material to surface-passivation, plasmonic enhancement, or doping. As expected, improving the optical properties of UC materials can lead to enhanced efficiency of PDs and photovoltaic devices.

Focused role of nanoparticles against COVID-19: Diagnosis and treatment.

The 2019 novel coronavirus (2019-nCoV; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has witnessed a rapid and global proliferation since its early identification in patients with severe pneumonia in Wuhan, China. As of 27th May 2020, 2019-nCoV cases have risen to >5 million, with confirmed deaths of 350,000. However, Coronavirus disease (COVID-19) diagnostic and treatment measures are yet to be fully unraveled, given the novelty of this particular coronavirus. Therefore, existing antiviral agents used for severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) were repurposed for COVID-19, taking their biological features into consideration. This study provides a concise review of the current and emerging detection and supervision technologies for SARS-CoV-2, which is the viral etiology of COVID19, and their performance characteristics, with emphasis on the novel Nano-based diagnostic tests (protein corona sensor array and magnetic levitation) and treatment measures (treatment protocols based on nano-silver colloids) for COVID-19.

Simple rapid stabilization method through citric acid modification for magnetite nanoparticles.

A highly stable and magnetized citric acid (CA)-functionalized iron oxide aqueous colloidal solution (Fe3O4@CA) was synthesized by using a simple and rapid method of one-step co-participation via a chemical reaction between Fe3+ and Fe2+ in a NaOH solution at 65 °C, followed by CA addition to functionalize the Fe3O4 surface in 25 min. The NPs were synthesized at lower temperatures and shortened time compared with conventional methods. Surface functionalization is highly suggested because bare Fe3O4 nanoparticles (Fe3O4 NPs) are frequently deficient due to their low stability and hydrophilicity. Hence, 19 nm-sized Fe3O4 NPs coated with CA (Fe3O4@CA) were synthesized, and their microstructure, morphology, and magnetic properties were characterized using X-ray diffraction, transmission electron microscopy, Zeta potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometer. CA successfully modified the Fe3O4 surface to obtain a stabilized (homogeneous and well dispersed) aqueous colloidal solution. The Zeta potential value of the as-prepared Fe3O4@CA increases from - 31 to - 45 mV. These CA-functionalized NPs with high magnetic saturation (54.8 emu/g) show promising biomedical applications.

Trastuzumab conjugated porphyrin-superparamagnetic iron oxide nanoparticle: A potential PTT-MRI bimodal agent for herceptin positive breast cancer.

BACKGROUND: Theranostic agents can combine photosensitizers and contrast agents into a single unit for photothermal therapy (PTT) and magnetic resonance imaging (MRI). The possibility of treating and diagnosing malignant cancers without any ionizing radiation could become an option. This study investigates the theranostic potential of Fe3O4 nanoparticles (IONs) for the diagnosis and treatment of cancer by developing a single integrated nanoprobe. METHODS: Oleylamin-coated IONs (ION-Ol) were synthesized and surface of the IONs was modified using protoporphyrin (PP) and trastuzumab (TZ) to develop the TZ-conjugated SPION-porphyrin [ION-PP-TZ]. The structure, morphology, size, and cytotoxicity of all samples were investigated using Fourier-transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM), X-ray powder diffraction (XRD), WST-1 assay, respectively. In addition to MRI and in vitro laser irradiation (808 nm, 200 mW) to determine the r2 values and photothermal ablation. RESULTS: The sizes of monodispersed nanoparticles were measured in rang 5.74-7.17 nm. No cytotoxicity was observed after incubating MCF 7 cells under various Fe concentrations of nanoparticles and theranostic agents. The transverse relaxation time of the protoporphyrin conjugated to IONs (52.32 mM-1s-1) exceeded that of ION-Ol and TZ-conjugated ION-PP. In addition, the in vitro photothermal ablation of ION-PP-TZ revealed a 74 % MCF 7 cell reduction after 10 min of at the highest Fe concentration (1.00 mg Fe/mL). CONCLUSIONS: In summary, the water-soluble ION-PP-TZ is a promising bimodal agent for the diagnosis and treatment of human epidermal growth factor receptor 2-positive breast cancer cells using a T2 MRI contrast agent and photothermal therapy.

Mechanisms of effective gold shell on Fe3O4 core nanoparticles formation using sonochemistry method.

Sonochemical synthesis (sonochemistry) is one of the most effective techniques of breaking down large clusters of nanoparticles (NPs) into smaller clusters or even individual NPs, which ensures their dispersibility (stability) in a solution over a long duration. This paper demonstrates the potential of sonochemistry becoming a valuable tool for the deposition of gold (Au) shell on iron oxide nanoparticles (Fe3O4 NPs) by explaining the underlying complex processes that control the deposition mechanism. This review summarizes the principles of the sonochemistry method and highlights the resulting phenomenon of acoustic cavitation and its associated physical, chemical and thermal effects. The effect of sonochemistry on the deposition of Au NPs on the Fe3O4 surface of various sizes is presented and discussed. A Vibra-Cell ultrasonic solid horn with tip size, frequency, power output of ½ inch, 20 kHz and 750 W respectively was used in core@shell synthesis. The sonochemical process was shown to affect the surface and structure of Fe3O4 NPs via acoustic cavitation, which prevents the agglomeration of clusters in a solution, resulting in a more stable dispersion. Deciphering the mechanism that governs the formation of Au shell on Fe3O4 core NPs has emphasized the potential of sonication in enhancing the chemical activity in solutions.