A bioanalytical assay for estimation of thymoquinone in rats cerebrospinal fluid and brain tissues of nasally administrated thymoquinone loaded lipo-polymeric nanoshells and its pharmacokinetic profiling.

Thymoquinone (TH) has been one of the major phytochemical used in the treatment of cancers since long time, especially in the management of glioblastoma multiforme (GBM). The formulation of lipo-polymeric nanoshells (LPNs) and their nasal delivery are fascinating approaches for overcoming the drawbacks of low solubility and poor bioavailability of TH. Hence targeting LPNs to the brain requires a validated bioanalytical method for the assessment of TH concentration in Cerebrospinal fluid (CSF) and brain tissue homogenates (BTH). Therefore, the current work focuses on the development and validation of high-performance liquid chromatography (HPLC) method in CSF by employing nasal simulated fluid (NSF) as one of the major components of the mobile phase. The developed method was checked for linearity in the range of 0.05 to 1.6 µg/mL, having an r2 value of 0.999 with mean % recovery >95% and % RSD values below <2.0%. The developed method gave a clear separation of TH at 6.021 ± 0.17 min with an internal standard at 4.102 ± 0.09 min and a CSF spike at 2.170 ± 0.12 min. The developed method assisted in determining the in-vitro and in-vivo drug release study of LPNs, pharmacokinetic profiling, qualitative in-vivo brain uptake study, in-vitro cellular uptake, and generating stability data of formulated LPNs proposed for intranasal administration in rats.

Hepatitis B Virus Neutralization with DNA Origami Nanoshells.

We demonstrate the use of DNA origami to create virus-trapping nanoshells that efficiently neutralize hepatitis B virus (HBV) in cell culture. By modification of the shells with a synthetic monoclonal antibody that binds to the HBV envelope, the effective neutralization potency per antibody is increased by approximately 100 times compared to using free antibodies. The improvements in neutralizing the virus are attributed to two factors: first, the shells act as a physical barrier that blocks the virus from interacting with host cells; second, the multivalent binding of the antibodies inside the shells lead to stronger attachment to the trapped virus, a phenomenon known as avidity. Pre-incubation of shells with HBV and simultaneous addition of both components separately to cells lead to comparable levels of neutralization, indicating rapid trapping of the virions by the shells. Our study highlights the potential of the DNA shell system to rationally create antivirals using components that, when used individually, show little to no antiviral effectiveness.

One-pot synthesized Au@Pt nanostars-based lateral flow immunoassay for colorimetric and photothermal dual-mode detection of SARS-CoV-2 nucleocapsid antibody.

In addition to confirming virus infection, quantitative identification of the antibodies to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) also evaluates persons immunity to guide personal protection. However, portable assays for fast and accurate quantification of SARS-CoV-2 antibodies remain challenging. In this work, we synthesized Au@Pt star-like nanoparticles (NPs) quickly and easily by a one-pot wet-chemical approach, allowing the stellate Au core to be partially decorated by Pt nanoshells. The nanoparticles were used as probe in a lateral flow immunoassay (LFIA) that operated in both colorimetric and photothermal dual modes, which could detect the antibodies to the SARS-CoV-2 nucleocapsid (N) protein with high sensitivity. Due to the sharp tips on the external region of nanostars and surface plasmon coupling effect between the Au core and Pt shell, the NIR absorption capacity and photothermal performance of these NPs were exceptional. Under optimal conditions, the colorimetric mode's detection limit for SARS-CoV-2 N protein antibody was 1 ng mL-1, which is significantly lower by 2-order of magnitude compared to commercially available colloidal gold strips. And the detection limit for the photothermal mode was as low as 24.91 pg mL-1, which was approximately 40-fold more sensitive than colorimetric detection. Moreover, the method demonstrated favorable specificity, reproducibility and stability. Finally, the approach was employed for the successful identification of actual serum samples. Therefore, the dual-mode LFIA can be applied for screening and tracking the early immunological reaction to SARS-CoV-2, and it has great promise for clinical application.

High-Throughput Synthesis of Nanogap-Rich Gold Nanoshells Using Dual-Channel Infusion System.

Gold nanoshells have been actively applied in industries beyond the research stage because of their unique optical properties. Although numerous methods have been reported for gold nanoshell synthesis, the labor-intensive and time-consuming production process is an issue that must be overcome to meet industrial demands. To resolve this, we report a high-throughput synthesis method for nanogap-rich gold nanoshells based on a core silica support (denoted as SiO2@Au NS), affording a 50-fold increase in scale by combining it with a dual-channel infusion pump system. By continuously dropping the reactant solution through the pump, nanoshells with closely packed Au nanoparticles were prepared without interparticle aggregation. The thickness of the gold nanoshells was precisely controlled at 2.3-17.2 nm by regulating the volume of the reactant solution added dropwise. Depending on the shell thickness, the plasmonic characteristics of SiO2@Au NS prepared by the proposed method could be tuned. Moreover, SiO2@Au NS exhibited surface-enhanced Raman scattering activity comparable to that of gold nanoshells prepared by a previously reported low-throughput method at the same reactant ratio. The results indicate that the proposed high-throughput synthesis method involving the use of a dual-channel infusion system will contribute to improving the productivity of SiO2@Au NS with tunable plasmonic characteristics.

Rapid quantitative PCR equipment using photothermal conversion of Au nanoshell.

The emergence of infectious diseases worldwide necessitates rapid and precise diagnostics. Using gold nanoshells in the PCR mix, we harnessed their unique photothermal properties in the near-infrared regime to attain efficient heating, reaching ideal photothermal PCR cycle temperature profile. Our photothermal PCR method expedited DNA amplification while retaining its detection sensitivity. Combining photothermal quantitative PCR with real-time fluorometry and non-invasive temperature measurement, we could amplify the target DNA within just 25 min, with a minimum detectable DNA amount of 50 picograms. This innovation in photothermal qPCR, leveraging the photothermal properties of gold nanoshells, will pave the way for immediate point-of-care diagnostics of nucleic acid biomarkers.

Gold nanoshells for prostate cancer treatment: evidence for deposition in abdominal organs.

PURPOSE: Gold-silica nanoshell therapy [AuroShells with subsequent focal laser therapy (AuroLase)] is an emerging targeted treatment modality for prostate cancer. We reviewed pre- and post-treatment unenhanced CT imaging to assess for retained gold-silica nanoshells in the abdomen and pelvis. METHODS: This single-institution retrospective study identified patients in the AuroLase pilot who underwent pre- and post-treatment unenhanced abdominopelvic CT. The attenuation, before and after gold-silica nanoshell administration, of the liver, spleen, pancreas, kidneys, prostate, blood pool, paraspinal musculature, and abnormal lymph nodes were manually measured by two readers. After inter-reader agreement was calculated using intraclass correlation (ICC), a permutation test was used to assess pre- and post-therapy attenuation differences. RESULTS: Four patients met the inclusion criteria. Mean age was 72.3 ± 5.9 years. Median time interval between pre-treatment CT and treatment, and between treatment and post-treatment CT, was 232 days and 236.5 days, respectively. The two readers' attenuation measurements had very high agreement (ICC = 0.99, p < 0.001). The highest differences in organ attenuation between pre- and post-therapy scans were seen in all four patients in the liver and spleen (liver increased by an average of 28.9 HU, p = 0.010; spleen increased by an average of 63.7 HU, p = 0.012). A single measured lymph node increased by an average of 58.9 HU. In the remainder of the measured sites, the change in attenuation from pre- to post-therapy scans ranged from -0.1 to 3.8 HU (p > 0.05). CONCLUSION: Increased attenuation of liver and spleen at CT can be an expected finding in patients who have received gold-silica nanoshell therapy.

Metal-Based Nanoparticles for Cardiovascular Diseases.

Globally, cardiovascular diseases (CVDs) are the leading cause of death and disability. While there are many therapeutic alternatives available for the management of CVDs, the majority of classic therapeutic strategies were found to be ineffective at stopping or significantly/additionally slowing the progression of these diseases, or they had unfavorable side effects. Numerous metal-based nanoparticles (NPs) have been created to overcome these limitations, demonstrating encouraging possibilities in the treatment of CVDs due to advancements in nanotechnology. Metallic nanomaterials, including gold, silver, and iron, come in various shapes, sizes, and geometries. Metallic NPs are generally smaller and have more specialized physical, chemical, and biological properties. Metal-based NPs may come in various forms, such as nanoshells, nanorods, and nanospheres, and they have been studied the most. Massive potential applications for these metal nanomaterial structures include supporting molecular imaging, serving as drug delivery systems, enhancing radiation-based anticancer therapy, supplying photothermal transforming effects for thermal therapy, and being compounds with bactericidal, fungicidal, and antiviral qualities that may be helpful for cardiovascular diseases. In this context, the present paper aims to review the applications of relevant metal and metal oxide nanoparticles in CVDs, creating an up-to-date framework that aids researchers in developing more efficient treatment strategies.

A Micrometric Transformer: Compositional Nanoshell Transformation of Fe3+ -Trimesic-Acid Complex with Concomitant Payload Release in Cell-in-Catalytic-Shell Nanobiohybrids.

Nanoencapsulation of living cells within artificial shells is a powerful approach for augmenting the inherent capacity of cells and enabling the acquisition of extrinsic functions. However, the current state of the field requires the development of nanoshells that can dynamically sense and adapt to environmental changes by undergoing transformations in form and composition. This paper reports the compositional transformation of an enzyme-embedded nanoshell of Fe3+ -trimesic acid complex to an iron phosphate shell in phosphate-containing media. The cytocompatible transformation allows the nanoshells to release functional molecules without loss of activities and biorecognition, while preserving the initial shell properties, such as cytoprotection. Demonstrations include the lysis and killing of Escherichia coli by lysozyme, and the secretion of interleukin-2 by Jurkat T cells in response to paracrine stimulation by antibodies. This work on micrometric Transformers will benefit the creation of cell-in-shell nanobiohybrids that can interact with their surroundings in active and adaptive ways.

Urease-Powered Micromotors with Spatially Selective Distribution of Enzymes for Capturing and Sensing Exosomes.

Enzyme-catalyzed micro/nanomotors (MNMs) exhibit tremendous potential for biological isolation and sensing, because of their biocompatibility, versatility, and ready access to biofuel. However, flow field generated by enzyme-catalyzed reactions might significantly hinder performance of surface-linked functional moieties, e.g., the binding interaction between MNMs and target cargos. Herein, we develop enzymatic micromotors with spatially selective distribution of urease to enable the independent operation of various modules and facilitate the capture and sensing of exosomes. When urease is modified into the motors' cavity, the flow field from enzyme catalysis has little effect on the exterior surface of the motors. The active motion and encapsulating urease internally result in enhancement of ∼35% and 18% in binding efficiency of target cargos, e.g., exosomes as an example here, compared to their static counterparts and moving micromotors with urease modified externally, respectively. Once exosomes are trapped, they can be transferred to a clean environment by the motors for Raman signal detection and/or identification using the surface Raman enhancement scattering (SERS) effect of coated gold nanoshell. The biocatalytic micromotors, achieving spatial separation between driving module and function module, offer considerable promise for future design of multifunctional MNMs in biomedicine and diagnostics.

Transition metal dichalcogenide coated gold nanoshells for highly effective photothermal therapy.

Transition metal dichalcogenides (TMD) coated gold nanoshells (GNSs), in addition to having low cytotoxicity and a biocompatibility value greater than graphene, exhibit strong light absorption in the near-infrared (NIR) region and high photothermal conversion efficiency. Using a quasi-static approach and bioheat equations, the optical and photothermal properties of GNSs coated with various TMDs are studied for treatment of skin cancer. Our findings show that the intensity of localized surface plasmon resonance (LSPR) peaks and their position in the extinction spectrum of nanoparticles (NPs) can be easily tuned within biological windows by varying the core radius, the gold shell thickness and the number of coating layers of the different TMDs. In order to engineer heat production at designated spatial locations of NPs, near electric field (NEF) enhancement is investigated. Moreover, the effect of laser intensity and the number of TMD layers on the temperature rise and the amount of thermal damage in skin tumor tissue and its surroundings are studied. Our results introduce GNSs with various TMD coatings as superlative nanoagents for photothermal therapy (PTT) applications.

Efficient sonochemical catalytic degradation of tetracycline using TiO2 fractured nanoshells.

Overexposure to antibiotics originating in wastewater has profound environmental and health implications. Conventional treatment methods are not fully effective in removing certain antibiotics, such as the commonly used antibiotic, tetracycline, leading to its accumulation in water catchments. Alternative antibiotic removal strategies are garnering attention, including sonocatalytic oxidative processes. In this work, we investigated the degradation of tetracycline using a combination of TiO2 fractured nanoshells (TFNs) and an advanced sonochemical reactor design. The study encompassed an examination of multiple process parameters to understand their effects on the degradation of tetracycline. These included tetracycline adsorption on TFNs, reaction time, initial tetracycline concentration, solvent pH, acoustic pressure amplitude, number of acoustic cycles, catalyst dosage, TFNs' reusability, and the impact of adjuvants such as light and H2O2. Though TFNs adsorbed tetracycline, the addition of ultrasound was able to degrade tetracycline completely (with 100% degradation) within six minutes. Under the optimal operating conditions, the proposed sonocatalytic system consumed 80% less energy compared to the values reported in recently published sonocatalytic research. It also had the lowest CO2 footprint when compared to the other sono-/photo-based technologies. This study suggests that optimizing the reaction system and operating the reaction under low power and at a lower duty cycle are effective in achieving efficient cavitation for sonocatalytic reactions.

Biotin-decorated hollow gold nanoshells for dual-modal imaging-guided NIR-II photothermal and radiosensitizing therapy toward breast cancer.

Radiotherapy (RT) is dominantly used in breast cancer therapy but is facing fierce side effects because of the limited difference between tumor and normal tissues in response to ionizing radiation. Herein, we construct a core-shell nanoparticle of UiO-66-NH2@AuNS. Then the solid gold shell was etched into hollow AuNS (HAuNS) and further modified with biotin-PEG-SH (PEG-bio) to obtain HAuNS@PEG-bio. HAuNS@PEG-bio demonstrates effective near infrared II (NIR-II) region photothermal therapy (PTT) performance, and the increase of temperature at the tumor site promotes the blood circulation to alleviate the hypoxia in the tumor microenvironment (TME). Meanwhile, HAuNS exhibits strong X-ray absorption and deposition ability due to the high atomic coefficient of elemental Au (Z = 79) and hollowed-out structure. Through the dual radiosensitization of the high atomic coefficient of Au and the hypoxia alleviation from PTT of HAuNS, the breast cancer cells could undergo immunogenic cell death (ICD) to activate the immune response. At the in vivo level, HAuNS@PEG-bio performs NIR-II photothermal, radiosensitization, and ICD therapies through cellular targeting, guided by infrared heat and CT imaging. This work highlights that the constructed biotin-decorated hollow gold nanoshell has a promising potential as a diagnostic and treatment integration reagents for the breast cancer.

Recent Advances in the Nanoshells Approach for Encapsulation of Single Probiotics.

The intestine, often referred to as the "second brain" of the human body, houses a vast microbial community that plays a crucial role in maintaining the host's balance and directly impacting overall health. Probiotics, a type of beneficial microorganism, offer various health benefits when consumed. However, probiotics face challenges such as acidic conditions in the stomach, bile acids, enzymes, and other adverse factors before they can colonize the intestinal tissues. At present, pills, dry powder, encapsulation, chemically modified bacteria, and genetically engineered bacteria have emerged as the preferred method for the stable and targeted delivery of probiotics. In particular, the use of nanoshells on the surface of single probiotics has shown promise in regulating their growth and differentiation. These nanoshells can detach from the probiotics' surface upon reaching the intestine, facilitating direct contact between the probiotics and intestinal mucosa. In this perspective, we provide an overview of the current developments in the formation of nanoshells mediated by single probiotics. We also discuss the advantages and disadvantages of different nanocoating strategies and explore future trends in probiotic protection.

High-density Au nanoshells assembled onto Fe3O4 nanoclusters for integrated enrichment and photothermal/colorimetric dual-mode detection of SARS-CoV-2 nucleocapsid protein.

Traditional lateral flow immunoassays (LFIA) suffer from insufficient sensitivity, difficulty for quantitation, and susceptibility to complex substrates, limiting their practical application. Herein, we developed a polyethylenimine (PEI)-mediated approach for assembling high-density Au nanoshells onto Fe3O4 nanoclusters (MagAushell) as LFIA labels for integrated enrichment and photothermal/colorimetric dual-mode detection of SARS-CoV-2 nucleocapsid protein (N protein). PEI layer served not only as "binders" to Fe3O4 nanoclusters and Au nanoshells, but also "barriers" to ambient environment. Thus, MagAushell not only combined magnetic and photothermal properties, but also showed good stability. With MagAushell, N protein was first separated and enriched from complex samples, and then loaded to the strip for detection. By observation of the color stripes, qualitative detection was performed with naked eye, and by measuring the temperature change under laser irradiation, quantification was attained free of sophisticated instruments. The introduction of Fe3O4 nanoclusters facilitated target purification and enrichment before LFIA, which greatly improved the anti-interference ability and increased the detection sensitivity by 2 orders compared with those without enrichment. Moreover, the high loading density of Au nanoshells on one Fe3O4 nanocluster enhanced the photothermal signal of the nanoprobe significantly, which could further increase the detection sensitivity. The photothermal detection limit reached 43.64 pg/mL which was 1000 times lower than colloidal gold strips. Moreover, this method was successfully applied to real samples, showing great application potential in practice. We envision that this LFIA could serve not only for SARS-CoV-2 detection but also as a general test platform for other biotargets in clinical samples.

Thermal dynamics of gold nanoshell dimers under femtosecond laser pulse irradiation: A numerical approach.

We present a numerical investigation of the photothermal response of gold nanoshell (AuNS) dimers when subjected to femtosecond laser pulse irradiation. The time-varying temperature fields for core-shell AuNS dimers are quantified by implementing finite element modeling, integrating the electromagnetic and thermal dual-physics simulations. Given the ultrafast nature of laser pulses, we employ a two-temperature model to accurately portray the energy transfer from excited electrons to the lattice system, a process typically completed post pulse-termination. The temporal analysis of the temperature in the AuNS and the surrounding medium, together with the spatial temperature distribution under different separation distances, elucidates the processes that drive the AuNS dimers' transient temperature distribution and heat dissipation. We report on the critical effects of geometrical parameters on the photothermal response, demonstrating that thinner shells maximize the total deposited energy per unit volume, resulting in increased temperature fields, while decreasing separation distances result in excessive field amplification due to plasmonic modes' production. Our robust numerical approach, enabling simulations with tunable material properties and configurations, may help design nanomaterials with desired features for photothermal cancer treatment and imaging.

In Situ Depletion-Guided Engineering of Nanoshell-like Gold Nanocluster Assemblies with Enhanced Peroxidase-like Nanozyme Activity.

Functional superstructures constructed from metal nanoclusters (MNCs) hold great promise in providing highly tunable photoluminescence (PL), catalytic activity, photothermal stability, and biological functionality. However, their controlled synthesis with well-defined size, structure, and properties remains a significant challenge. Herein, we introduce a novel approach that combines depletion attraction and thermal activation to induce the in situ formation of spherical superclusters (AuSCs) from Au(I)-thiolate complexes within the assembly. Extensive characterization and electron tomographic reconstruction reveal that Au(I)-thiolate complexes can be sequentially transitioned into metallic Au0, resulting in hollow nanoshell-like structures with consistent size (∼110 nm) and diverse shell configurations. Our results demonstrate that AuSCs with thinner shells, containing a high concentration of Au(I)-thiolate complexes, exhibit the highest PL, while AuSCs with thicker shells, containing high concentrations of metallic gold atoms and low ligand density, show remarkable peroxidase-like nanozyme activity in the 3,3',5,5'-tetramethylbenzidine (TMB) oxidation reaction.

Monodisperse Sub-100 nm Au Nanoshells for Low-Fluence Deep-Tissue Photoacoustic Imaging.

Nanoparticles with high absorption cross sections will advance therapeutic and bioimaging nanomedicine technologies. While Au nanoshells have shown great promise in nanomedicine, state-of-the-art synthesis methods result in scattering-dominant particles, mitigating their efficacy in absorption-based techniques that leverage the photothermal effect, such as photoacoustic (PA) imaging. We introduce a highly reproducible synthesis route to monodisperse sub-100 nm Au nanoshells with an absorption-dominant optical response. Au nanoshells with 48 nm SiO2 cores and 7 nm Au shells show a 14-fold increase in their volumetric absorption coefficient compared to commercial Au nanoshells with dimensions commonly used in nanomedicine. PA imaging with Au nanoshell contrast agents showed a 50% improvement in imaging depth for sub-100 nm Au nanoshells compared with the smallest commercially available nanoshells in a turbid phantom. Furthermore, the high PA signal at low fluences, enabled by sub-100 nm nanoshells, will aid the deployment of low-cost, low-fluence light-emitting diodes for PA imaging.

Inhibiting HER3 Hyperphosphorylation in HER2-Overexpressing Breast Cancer through Multimodal Therapy with Branched Gold Nanoshells.

Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+ /HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrier.

Synthetic Cell Armor Made of DNA Origami.

The bioengineering applications of cells, such as cell printing and multicellular assembly, are directly limited by cell damage and death due to a harsh environment. Improved cellular robustness thus motivates investigations into cell encapsulation, which provides essential protection. Here we target the cell-surface glycocalyx and cross-link two layers of DNA nanorods on the cellular plasma membrane to form a modular and programmable nanoshell. We show that the DNA origami nanoshell modulates the biophysical properties of cell membranes by enhancing the membrane stiffness and lowering the lipid fluidity. The nanoshell also serves as armor to protect cells and improve their viability against mechanical stress from osmotic imbalance, centrifugal forces, and fluid shear stress. Moreover, it enables mediated cell-cell interactions for effective and robust multicellular assembly. Our results demonstrate the potential of the nanoshell, not only as a cellular protection strategy but also as a platform for cell and cell membrane manipulation.

Effect of nanoshell geometries, sizes, and quantum emitter parameters on the sensitivity of plasmon-exciton hybrid nanoshells for sensing application.

A proposed nanosensor based on hybrid nanoshells consisting of a core of metal nanoparticles and a coating of molecules is simulated by plasmon-exciton coupling in semi classical approach. We study the interaction of electromagnetic radiation with multilevel atoms in a way that takes into account both the spatial and the temporal dependence of the local fields. Our approach has a wide range of applications, from the description of pulse propagation in two-level media to the elaborate simulation of optoelectronic devices, including sensors. We have numerically solved the corresponding system of coupled Maxwell-Liouville equations using finite difference time domain (FDTD) method for different geometries. Plasmon-exciton hybrid nanoshells with different geometries are designed and simulated, which shows more sensitive to environment refractive index (RI) than nanosensor based on localized surface plasmon. The effects of nanoshell geometries, sizes, and quantum emitter parameters on the sensitivity of nanosensors to changes in the RI of the environment were investigated. It was found that the cone-like nanoshell with a silver core and quantum emitter shell had the highest sensitivity. The tapered shape of the cone like nanoshell leads to a higher density of plasmonic excitations at the tapered end of the nanoshell. Under specific conditions, two sharp, deep LSPR peaks were evident in the scattering data. These distinguishing features are valuable as signatures in nanosensors requiring fast, noninvasive response.