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1.
ACS Appl Bio Mater ; 7(6): 4102-4115, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758756

RESUMO

The diatom's frustule, characterized by its rugged and porous exterior, exhibits a remarkable biomimetic morphology attributable to its highly ordered pores, extensive surface area, and unique architecture. Despite these advantages, the toxicity and nonbiodegradable nature of silica-based organisms pose a significant challenge when attempting to utilize these organisms as nanotopographically functionalized microparticles in the realm of biomedicine. In this study, we addressed this limitation by modulating the chemical composition of diatom microparticles by modulating the active silica metabolic uptake mechanism while maintaining their intricate three-dimensional architecture through calcium incorporation into living diatoms. Here, the diatom Thalassiosira weissflogii was chemically modified to replace its silica composition with a biodegradable calcium template, while simultaneously preserving the unique three-dimensional (3D) frustule structure with hierarchical patterns of pores and nanoscale architectural features, which was evident by the deposition of calcium as calcium carbonate. Calcium hydroxide is incorporated into the exoskeleton through the active mechanism of calcium uptake via a carbon-concentrating mechanism, without altering the microstructure. Our findings suggest that calcium-modified diatoms hold potential as a nature-inspired delivery system for immunotherapy through antibody-specific binding.


Assuntos
Materiais Biocompatíveis , Cálcio , Diatomáceas , Teste de Materiais , Tamanho da Partícula , Diatomáceas/metabolismo , Diatomáceas/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/metabolismo , Cálcio/metabolismo , Cálcio/química , Sistemas de Liberação de Medicamentos , Propriedades de Superfície , Dióxido de Silício/química , Porosidade
2.
Sensors (Basel) ; 24(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38339520

RESUMO

To ensure safe, secure, and efficient advanced air mobility (AAM) operations, an AAM surveillance network is needed to detect and track AAM traffic. Additionally, a cloud-based surveillance data collection, monitoring, and distribution center is needed, where AAM operators and service suppliers, law enforcement agencies, correctional facilities, and municipalities can subscribe to receiving relevant AAM traffic data to plan and monitor AAM operations. In this work, we developed an optimization model to design a surveillance sensor network for AAM that minimizes the total sensor cost while providing full coverage in the desired region of operation, considering terrain types of that region, terrain-based sensor detection probabilities, and meeting the minimum detection probability requirement. Moreover, we present a framework for the low altitude surveillance information clearinghouse (LASIC), connected to the optimized AAM surveillance network for receiving live surveillance feed. Additionally, we conducted a cost-benefit analysis of the AAM surveillance network and LASIC to justify an investment in it. We examine six potential types of AAM sensors and homogeneous and heterogeneous network types. Our analysis reveals the sensor types that are the most profitable options for detecting cooperative and non-cooperative aircraft. According to the findings, heterogeneous networks are more cost-effective than homogeneous sensor networks. Based on the sensitivity analysis, changes in parameters such as subscription fees, the number of subscribers, sensor detection probabilities, and the minimum required detection probability significantly impact the surveillance network design and cost-benefit analysis.

3.
Cells ; 13(2)2024 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-38247879

RESUMO

This comprehensive review explores the complex role of cofilin, an actin-binding protein, across various neurodegenerative diseases (Alzheimer's, Parkinson's, schizophrenia, amyotrophic lateral sclerosis (ALS), Huntington's) and stroke. Cofilin is an essential protein in cytoskeletal dynamics, and any dysregulation could lead to potentially serious complications. Cofilin's involvement is underscored by its impact on pathological hallmarks like Aß plaques and α-synuclein aggregates, triggering synaptic dysfunction, dendritic spine loss, and impaired neuronal plasticity, leading to cognitive decline. In Parkinson's disease, cofilin collaborates with α-synuclein, exacerbating neurotoxicity and impairing mitochondrial and axonal function. ALS and frontotemporal dementia showcase cofilin's association with genetic factors like C9ORF72, affecting actin dynamics and contributing to neurotoxicity. Huntington's disease brings cofilin into focus by impairing microglial migration and influencing synaptic plasticity through AMPA receptor regulation. Alzheimer's, Parkinson's, and schizophrenia exhibit 14-3-3 proteins in cofilin dysregulation as a shared pathological mechanism. In the case of stroke, cofilin takes center stage, mediating neurotoxicity and neuronal cell death. Notably, there is a potential overlap in the pathologies and involvement of cofilin in various diseases. In this context, referencing cofilin dysfunction could provide valuable insights into the common pathologies associated with the aforementioned conditions. Moreover, this review explores promising therapeutic interventions, including cofilin inhibitors and gene therapy, demonstrating efficacy in preclinical models. Challenges in inhibitor development, brain delivery, tissue/cell specificity, and long-term safety are acknowledged, emphasizing the need for precision drug therapy. The call to action involves collaborative research, biomarker identification, and advancing translational efforts. Cofilin emerges as a pivotal player, offering potential as a therapeutic target. However, unraveling its complexities requires concerted multidisciplinary efforts for nuanced and effective interventions across the intricate landscape of neurodegenerative diseases and stroke, presenting a hopeful avenue for improved patient care.


Assuntos
Fatores de Despolimerização de Actina , Doença de Alzheimer , Esclerose Lateral Amiotrófica , Doença de Parkinson , Acidente Vascular Cerebral , Humanos , alfa-Sinucleína , Acidente Vascular Cerebral/metabolismo
4.
Nanoscale ; 15(38): 15686-15699, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37724853

RESUMO

Localized heat generation from manganese iron oxide nanoparticles (MIONPs) conjugated with chemotherapeutics under the exposure of an alternating magnetic field (magneto-chemotherapy) can revolutionize targeted breast cancer therapy. On the other hand, the lack of precise control of local temperature and adequate MIONP distribution in laboratory settings using the conventional two-dimensional (2D) cellular models has limited its further translation in tumor sites. Our current study explored advanced 3D in vitro tumor models as a promising alternative to replicate the complete range of tumor characteristics. Specifically, we have focused on investigating the effectiveness of MIONP-based magneto-chemotherapy (MCT) as an anticancer treatment in a 3D breast cancer model. To achieve this, chitosan-coated MIONPs (CS-MIONPs) are synthesized and functionalized with an anticancer drug (doxorubicin) and a tumor-targeting aptamer (AS1411). CS-MIONPs with a crystallite size of 16.88 nm and a specific absorption rate (SAR) of 181.48 W g-1 are reported. In vitro assessment of MCF-7 breast cancer cell lines in 2D and 3D cell cultures demonstrated anticancer activity. In the 2D and 3D cancer models, the MIONP-mediated MCT reduced cancer cell viability to about 71.48% and 92.2%, respectively. On the other hand, MIONP-mediated MCT under an AC magnetic field diminished spheroids' viability to 83.76 ± 2%, being the most promising therapeutic modality against breast cancer.

5.
ACS Omega ; 8(31): 27845-27861, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37576695

RESUMO

Brain cancer is one of those few cancers with very high mortality and low five-year survival rate. First and foremost reason for the woes is the difficulty in diagnosing and monitoring the progression of brain tumors both benign and malignant, noninvasively and in real time. This raises a need in this hour for a tool to diagnose the tumors in the earliest possible time frame. On the other hand, Raman spectroscopy which is well-known for its ability to precisely represent the molecular markers available in any sample given, including biological ones, with great sensitivity and specificity. This has led to a number of studies where Raman spectroscopy has been used in brain tumors in various ways. This review article highlights the fundamentals of Raman spectroscopy and its types including conventional Raman, SERS, SORS, SRS, CARS, etc. are used in brain tumors for diagnostics, monitoring, and even theragnostics, collating all the major works in the area. Also, the review explores how Raman spectroscopy can be even more effectively used in theragnostics and the clinical level which would make them a one-stop solution for all brain cancer needs in the future.

6.
Langmuir ; 39(20): 7046-7056, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37162149

RESUMO

A simple noninvasive measurement method which allows one to determine the trapped charge in a biocompatible hydroxyapatite dielectric is developed. The hydroxyapatite samples are charged by electron beam with energy 30 keV and total irradiated charge ranging from 2 × 10-9 C to 2 × 10-7 C. The value of the trapped charge is determined by analyzing the shape change of a liquid droplet hanging from a needle in proximity of the charged sample surface. The shape change of the pendant drop in the field of gravity is commonly utilized in the measurements of the surface free tension (SFT) of liquids. The external electric field leads to a further modification of the droplet shape and to an effective change of the SFT. The change of the SFT as a function of distance between the droplet and sample and the critical distance at which the droplet detaches from the needle are measured for various values of the irradiated charge. These two quantities are also derived theoretically by considering the trapped charge as a single fitting parameter. We can thus determine the trapped charge in two independent noninvasive ways. It is noteworthy that our method is easily implementable into the standard pendant drop setups. As a practical application of the method, a long-term charge stability of the charged hydroxyapatite is demonstrated, thus paving the way toward quantitative studies of its bioactivity in dependence on the value of the trapped charge.

7.
RSC Adv ; 13(4): 2718-2726, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36741155

RESUMO

Measurement of the surface free energy (SFE) of a material allows the prediction of its adhesion properties. Materials can have microscale or sub-microscale surface inhomogeneities, engineered or random, which affect the surface macroscopic behaviour. However, quantitative characterization of the SFE at such length scales remains challenging in view of the variety of instruments and techniques available, the poor knowledge of critical variables and parameters during measurements and the need for appropriate contact models to derive the SFE from the measurements. Failure to characterize adhesion correctly may result in defective components or lengthy process optimization costing billions to industry. Conversely, for planar and homogeneous surfaces, contact angle (CA) measurements are standardized and allow for calculating the SFE using for example the Owen-Wendt model, relying only on the properties of the probing liquids. As such, we assessed and report here a method to correlate quantitative measurements of force-distance curves made with an atomic force microscope (AFM) and with silica and polystyrene (PS) colloidal probe pairs, with quantitative CA measurements and CA-derived SFE values. We measured five surfaces (mica, highly oriented pyrolytic graphite, thermally grown silica on silicon, silicon, and silicon with a super-hydrophobic coating), ranging from hydrophilic to super-hydrophobic, and found an excellent classification of the AFM measurements when these are represented by a set of principal components (PCs), and when both silica and PS colloidal probes are considered together. A regression of the PCs onto the CA measurements allows recovery of the SFE at the length scale of the colloidal probes, which is here ca. 1 micron. We found that once the PC-regression model is built, test sets of only ten AFM force-distance curves are sufficient to predict the local SFE with the calibrated silica and PS colloidal probes.

8.
ACS Omega ; 7(48): 44187-44198, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36506172

RESUMO

Optimization of manganese-substituted iron oxide nanoferrites having the composition Mn x Fe1-x Fe2O4 (x = 0-1) has been achieved by the chemical co-precipitation method. The crystallite size and phase purity were analyzed from X-ray diffraction. With increases in Mn2+ concentration, the crystallite size varies from 5.78 to 9.94 nm. Transmission electron microscopy (TEM) analysis depicted particle sizes ranging from 10 ± 0.2 to 13 ± 0.2 nm with increasing Mn2+ substitution. The magnetization (M s) value varies significantly with increasing Mn2+ substitution. The variation in the magnetic properties may be attributed to the substitution of Fe2+ ions by Mn2+ ions inducing a change in the superexchange interaction between the A and B sublattices. The self-heating characteristics of Mn x Fe1-x Fe2O4 (x = 0-1) nanoparticles (NPs) in an AC magnetic field are evaluated by specific absorption rate (SAR) and intrinsic loss power, both of which are presented with varying NP composition, NP concentration, and field amplitudes. Mn0.75Fe0.25Fe2O4 exhibited superior induction heating properties in terms of a SAR of 153.76 W/g. This superior value of SAR with an optimized Mn2+ content is presented in correlation with the cation distribution of Mn2+ in the A or B position in the Fe3O4 structure and enhancement in magnetic saturation. These optimized Mn0.75Fe0.25Fe2O4 NPs can be used as a promising candidate for hyperthermia applications.

9.
ACS Omega ; 7(24): 20656-20665, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35755394

RESUMO

Gold nanoparticles (GNPs) possess various interesting plasmonic properties that can provide a variety of diagnostic and therapeutic functionalities for biomedical applications. Compared to other inorganic metal nanoparticles (NPs), GNPs are less toxic and more biocompatible. However, the in vivo toxicity of gold nanoparticles on humans can be significant due to the size effect. This work aims to study the effect of multiple doses of small-size (≈20 nm) GNPs on the vital organs of Wistar rats. The study includes the oxidative stress in vital organs (liver, brain, and kidney) caused by GNPs and histopathology analysis. The rats were given a single caudal injection of NPs dispersed in PBS at 25, 50, 100, and 250 mg/kg of body weight. After sacrifice, both plasma and organs were collected for the determination of oxidant/antioxidant markers and histological studies. Our data show the high sensitivity of oxidative stress parameters to the GNPs in the brain, liver, and kidneys. However, the response to this stress is different between the organs and depends upon the antioxidant defense, where GSH levels control the MDA and PCO levels. Histological alterations are mild at 25, 50, and 100 mg/kg but significant at higher concentrations of 250 mg/kg. Therefore, histological impairments are shown to be dependent on the dose of GNPs. The results contribute to the understanding of oxidative stress and cellular interaction induced by nanoparticles.

12.
Nano Lett ; 22(4): 1504-1510, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35112876

RESUMO

Temporal and spectral behaviors of plasmons determine their ability to enhance the characteristics of metamaterials tailored to a wide range of applications, including electric-field enhancement, hot-electron injection, sensing, as well as polarization and angular momentum manipulation. We report a dark-field (DF) polarimetry experiment on single particles with incident circularly polarized light in which gold nanoparticles scatter with opposite handedness at visible wavelengths. Remarkably, for silvered nanoporous silica microparticles, the handedness conversion occurs at longer visible wavelengths, only after adsorption of molecules on the silver. Finite element analysis (FEA) allows matching the circular polarization (CP) conversion to dominant quadrupolar contributions, determined by the specimen size and complex susceptibility. We hypothesize that the damping accompanying the adsorption of molecules on the nanostructured silver facilitates the CP conversion. These results offer new perspectives in molecule sensing and materials tunability for light polarization conversion and control of light spin angular momentum at submicroscopic scale.

13.
J Am Chem Soc ; 144(8): 3468-3476, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35073071

RESUMO

The apparent piezoelectricity of biological materials is not yet fully understood at the molecular level. In particular, dynamic noncovalent interactions, such as host-guest binding, are not included in the classical piezoelectric model, which limits the rational design of eco-friendly piezoelectric supramolecular materials. Here, inspired by the conformation-dependent mechanoresponse of the Piezo channel proteins, we show that guest-host interactions can amplify the electromechanical response of a conformationally mobile peptide metal-organic framework (MOF) based on the endogenous carnosine dipeptide, demonstrating a new type of adaptive piezoelectric supramolecular material. Density functional theory (DFT) predictions validated by piezoresponse force microscopy (PFM) measurements show that directional alignment of the guest molecules in the host carnosine-zinc peptide MOF channel determines the macroscopic electromechanical properties. We produce stable, robust 1.4 V open-circuit voltage under applied force of 25 N with a frequency of 0.1 Hz. Our findings demonstrate that the regulation of host-guest interactions could serve as an efficient method for engineering sustainable peptide-based power generators.


Assuntos
Carnosina , Estruturas Metalorgânicas , Microscopia de Força Atômica , Conformação Molecular , Compostos Orgânicos
14.
Cryst Growth Des ; 21(10): 5818-5827, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34650339

RESUMO

Cocrystallization of two or more molecular compounds can dramatically change the physicochemical properties of a functional molecule without the need for chemical modification. For example, coformers can enhance the mechanical stability, processability, and solubility of pharmaceutical compounds to enable better medicines. Here, we demonstrate that amino acid cocrystals can enhance functional electromechanical properties in simple, sustainable materials as exemplified by glycine and sulfamic acid. These coformers crystallize independently in centrosymmetric space groups when they are grown as single-component crystals but form a noncentrosymmetric, electromechanically active ionic cocrystal when they are crystallized together. The piezoelectricity of the cocrystal is characterized using techniques tailored to overcome the challenges associated with measuring the electromechanical properties of soft (organic) crystals. The piezoelectric tensor of the cocrystal is mapped using density functional theory (DFT) computer models, and the predicted single-crystal longitudinal response of 2 pC/N is verified using second-harmonic generation (SHG) and piezoresponse force microscopy (PFM). The experimental measurements are facilitated by polycrystalline film growth that allows for macroscopic and nanoscale quantification of the longitudinal out-of-plane response, which is in the range exploited in piezoelectric technologies made from quartz, aluminum nitride, and zinc oxide. The large-area polycrystalline film retains a damped response of ≥0.2 pC/N, indicating the potential for application of such inexpensive and eco-friendly amino acid-based cocrystal coatings in, for example, autonomous ambient-powered devices in edge computing.

15.
Acta Biomater ; 136: 389-401, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34624554

RESUMO

Modelling of needle insertion in soft tissue has developed significant interest in recent years due to its application in robot-assisted minimally invasive surgeries such as biopsies and brachytherapy. However, this type of surgery requires real-time feedback and processing which complex computational models may not be able to provide. In contrast to the existing mechanics-based kinetic models, a simple multilayer tissue model using a Coupled Eulerian Lagrangian based Finite Element method has been developed using the dynamic principle. The model simulates the needle motion for flexible hollow bevel-angled needle (15° and 30°, 22 Gauge) insertion into porcine liver tissue, which includes material parameters obtained from unconfined compression testing of porcine liver tissue. To validate simulation results, needle insertion force and cutting force within porcine liver tissue were compared with corresponding experimental results obtained from a custom-built needle insertion system. For the 15° and 30° bevel-angle needles, the percentage error for cutting force (mean) of each needle compared to computational model, were 18.7% and 11.9% respectively. Varying the needle bevel angle from 30° to 15° results in an increase of the cutting force, but insertion force does not vary among the tested bevel angles. The validation of this computationally efficient multilayer Finite Element model can help engineers to better understand the biomechanical behaviour of medical needle inside soft biological tissue. Ultimately, this multilayer approach can help advance state-of-art clinical applications such as robot-assisted surgery that requires real-time feedback and processing. STATEMENT OF SIGNIFICANCE: The significance of the work is in confirming the effectiveness of multilayer material based finite element (FE) method to model biopsy needle insertion into soft biological porcine liver tissue. A multilayer Coupled Eulerian Lagrangian (CEL) based FE modelling technique allowed testing of heterogeneous, non-linear viscoelastic porcine liver tissue in a system, so direct comparison of needle tissue interaction forces on the intrinsic material (tissue) behaviour could be made. To the best of the authors' knowledge, the present research investigates for the first time modelling of a three dimensional (3D) hollow needle insertion using a multilayer stiffness model of biological tissue using FE based CEL method and presents a comparison of simulation results with experimental data.


Assuntos
Agulhas , Punções , Animais , Biópsia por Agulha , Simulação por Computador , Fígado , Modelos Biológicos , Suínos
16.
Adv Mater ; 33(40): e2008788, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34423493

RESUMO

Tendon disease constitutes an unmet clinical need and remains a critical challenge in the field of orthopaedic surgery. Innovative solutions are required to overcome the limitations of current tendon grafting approaches, and bioelectronic therapies show promise in treating musculoskeletal diseases, accelerating functional recovery through the activation of tissue regeneration-specific signaling pathways. Self-powered bioelectronic devices, particularly piezoelectric materials, represent a paradigm shift in biomedicine, negating the need for battery or external powering and complementing existing mechanotherapy to accelerate the repair processes. Here, the dynamic response of tendon cells to a piezoelectric collagen-analogue scaffold comprised of aligned nanoscale fibers made of the ferroelectric material poly(vinylidene fluoride-co-trifluoroethylene) is shown. It is demonstrated that motion-powered electromechanical stimulation of tendon tissue through piezo-bioelectric device results in ion channel modulation in vitro and regulates specific tissue regeneration signaling pathways. Finally, the potential of the piezo-bioelectronic device in modulating the progression of tendinopathy-associated processes in vivo, using a rat Achilles acute injury model is shown. This study indicates that electromechanical stimulation regulates mechanosensitive ion channel sensitivity and promotes tendon-specific over non-tenogenic tissue repair processes.


Assuntos
Eletrônica , Canais Iônicos/metabolismo , Tendões/fisiologia , Engenharia Tecidual/métodos , Animais , Colágeno/química , Módulo de Elasticidade , Estimulação Elétrica , Hidrocarbonetos Fluorados/química , Ratos , Regeneração/fisiologia , Transdução de Sinais , Tendões/citologia , Engenharia Tecidual/instrumentação , Alicerces Teciduais/química , Compostos de Vinila/química
17.
J Am Chem Soc ; 143(24): 9060-9069, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34115491

RESUMO

Nanostructures that are inaccessible through spontaneous thermodynamic processes may be formed by supramolecular self-assembly under kinetic control. In the past decade, the dynamics of pathway complexity in self-assembly have been elucidated through kinetic models based on aggregate growth by sequential monomer association and dissociation. Immiscible liquid-liquid interfaces are an attractive platform to develop well-ordered self-assembled nanostructures, unattainable in bulk solution, due to the templating interaction of the interface with adsorbed molecules. Here, we report time-resolved in situ UV-vis spectroscopic observations of the self-assembly of zinc(II) meso-tetrakis(4-carboxyphenyl)porphyrin (ZnTPPc) at an immiscible aqueous-organic interface. We show that the kinetically favored metastable J-type nanostructures form quickly, but then transform into stable thermodynamically favored H-type nanostructures. Numerical modeling revealed two parallel and competing cooperative pathways leading to the different porphyrin nanostructures. These insights demonstrate that pathway complexity is not unique to self-assembly processes in bulk solution and is equally valid for interfacial self-assembly. Subsequently, the interfacial electrostatic environment was tuned using a kosmotropic anion (citrate) in order to influence the pathway selection. At high concentrations, interfacial nanostructure formation was forced completely down the kinetically favored pathway, and only J-type nanostructures were obtained. Furthermore, we found by atomic force microscopy and scanning electron microscopy that the J- and H-type nanostructures obtained at low and high citric acid concentrations, respectively, are morphologically distinct, which illustrates the pathway-dependent material properties.

18.
Nat Commun ; 12(1): 2634, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976129

RESUMO

Realization of a self-assembled, nontoxic and eco-friendly piezoelectric device with high-performance, sensitivity and reliability is highly desirable to complement conventional inorganic and polymer based materials. Hierarchically organized natural materials such as collagen have long been posited to exhibit electromechanical properties that could potentially be amplified via molecular engineering to produce technologically relevant piezoelectricity. Here, by using a simple, minimalistic, building block of collagen, we fabricate a peptide-based piezoelectric generator utilising a radically different helical arrangement of Phe-Phe-derived peptide, Pro-Phe-Phe and Hyp-Phe-Phe, based only on proteinogenic amino acids. The simple addition of a hydroxyl group increases the expected piezoelectric response by an order of magnitude (d35 = 27 pm V-1). The value is highest predicted to date in short natural peptides. We demonstrate tripeptide-based power generator that produces stable max current >50 nA and potential >1.2 V. Our results provide a promising device demonstration of computationally-guided molecular engineering of piezoelectricity in peptide nanotechnology.


Assuntos
Fontes de Energia Bioelétrica , Materiais Biomiméticos/química , Biomimética/métodos , Engenharia Química/métodos , Oligopeptídeos/química , Materiais Biomiméticos/metabolismo , Colágeno/química , Desenho Assistido por Computador , Microscopia Eletrônica de Transmissão , Simulação de Dinâmica Molecular , Oligopeptídeos/metabolismo , Conformação Proteica em alfa-Hélice , Reprodutibilidade dos Testes , Difração de Raios X
19.
Nanomaterials (Basel) ; 11(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803430

RESUMO

Magnetic-plasmonic, Fe3O4-Au, core-shell nanoparticles are popular in many applications, most notably in therapeutics and diagnostics, and thus, the imaging of these nanostructures in biological samples is of high importance. These nanostructures are typically imaged in biological material by dark field scatter imaging, which requires an even distribution of nanostructures in the sample and, therefore, high nanoparticle doses, potentially leading to toxicology issues. Herein, we explore the nonlinear optical properties of magnetic nanoparticles coated with various thicknesses of gold using the open aperture z-scan technique to determine the nonlinear optical properties and moreover, predict the efficacy of the nanostructures in nonlinear imaging. We find that the magnetic nanoparticles coated with gold nanoseeds and thinner gold shells (ca. 4 nm) show the largest nonlinear absorption coefficient ß and imaginary part of the third-order susceptibility Im χ(3), suggesting that these nanostructures would be suitable contrast agents. Next, we combine laser dark field microscopy and epi-detected coherent anti-Stokes Raman (CARS) microscopy to image the uptake of magnetic-plasmonic nanoparticles in human pancreatic cancer cells. We show the epi-detected CARS technique is suitable for imaging of the magnetic-plasmonic nanoparticles without requiring a dense distribution of nanoparticles. This technique achieves superior nanoparticle contrasting over both epi-detected backscatter imaging and transmission dark field imaging, while also attaining label-free chemical contrasting of the cell. Lastly, we show the high biocompatibility of the Fe3O4 nanoparticles with ca. 4-nm thick Au shell at concentrations of 10-100 µg/mL.

20.
Eur J Pharm Sci ; 159: 105702, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33429045

RESUMO

Due to the complexity in the interactions of variables and mechanisms leading to blend segregation, quantifying the segregation propensity of an Active Pharmaceutical Ingredient (API) has been challenging. A high-throughput segregation risk prediction workflow for early drug product development has been developed based on the dispensing mechanism of automated powder dispensing technology. The workflow utilized liquid handling robots and high-performance liquid chromatography (HPLC) with a well-plate autosampler for sample preparation and analysis. Blends containing three different APIs of varying concentrations and particle sizes of different constituents were evaluated through this automated workflow. The workflow enabled segregation evaluation of different API blends in very small quantities (~7g) compared to other common segregation testers that consume hundreds of grams. Segregation patterns obtained were well explained with vibration induced percolation-based segregation phenomena. Segregation risk was translated quantitatively using relative standard deviation (RSD) calculations, and the results matched well with large-scale segregation studies. The applied approach increased the throughput, introduced a simple and clean walk-up method with minimized equipment space and API exposures to conduct segregation studies. Results obtained can provide insights about optimizing particle size distributions, as well as selecting appropriate formulation constituents and secondary processing steps in early drug product development when the amount of available API is very limited.


Assuntos
Química Farmacêutica , Tecnologia Farmacêutica , Excipientes , Pós , Tecnologia
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