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- C60 fullerene (2)
- apoptosis (2)
- photonic integrated circuits (2)
- sonodynamic therapy (2)
- surface plasmon resonance (2)
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Cancer sonodynamic therapy (SDT) is the therapeutic strategy of a high-frequency ultrasound (US) combined with a special sonosensitizer that becomes cytotoxic upon US exposure. The growing number of newly discovered sonosensitizers and custom US in vitro treatment solutions push the SDT field into a need for systemic studies and reproducible in vitro experimental set-ups. In the current research, we aimed to compare two of the most used and suitable SDT in vitro set-ups—“sealed well” and “transducer in well”—in one systematic study. We assessed US pressure, intensity, and temperature distribution in wells under US irradiation. Treatment efficacy was evaluated for both set-ups towards cancer cell lines of different origins, treated with two promising sonosensitizer candidates—carbon nanoparticle C60 fullerene (C60) and herbal alkaloid berberine. C60 was found to exhibit higher sonotoxicity toward cancer cells than berberine. The higher efficacy of sonodynamic treatment with a “transducer in well” set-up than a “sealed well” set-up underlined its promising application for SDT in vitro studies. The “transducer in well” set-up is recommended for in vitro US treatment investigations based on its US-field homogeneity and pronounced cellular effects. Moreover, SDT with C60 and berberine could be exploited as a promising combinative approach for cancer treatment.
Thin polytetrafluoroethylene (PTFE) films are produced by deposition from a gas phase by two methods: electron-enhanced vacuum deposition (EVD) and EVD + low-temperature plasma (LTP). Structure, morphology, and composition of the films are studied by IR spectroscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. They are close to the structure of bulk PTFE. The roughness of the films’ surface is changed with gas pressure and LTP power variations. Films are transparent from UV to near-infrared regions. Refractive and extinction indices and their anisotropy are measured by spectral ellipsometry. They are tuned by variations of deposition conditions. Hardness and Young modulus of the films are increased if EVD + low power LTP is used for film deposition. Use of EVD + LTP also increases thermal stability of the films. Contact angle of the films corresponds to the bulk PTFE. The PTFE molecules oriented are preferentially in perpendicular direction to the substrate surface.
The acoustic pressure waves of ultrasound (US) not only penetrate biological tissues deeper than light, but they also generate light emission, termed sonoluminescence. This promoted the idea of its use as an alternative energy source for photosensitizer excitation. Pristine C60 fullerene (C60), an excellent photosensitizer, was explored in the frame of cancer sonodynamic therapy (SDT). For that purpose, we analyzed C60 effects on human cervix carcinoma HeLa cells in combination with a low-intensity US treatment. The time-dependent accumulation of C60 in HeLa cells reached its maximum at 24 h (800 ± 66 ng/106 cells). Half of extranuclear C60 is localized within mitochondria. The efficiency of the C60 nanostructure’s sonoexcitation with 1 MHz US was tested with cell-based assays. A significant proapoptotic sonotoxic effect of C60 was found for HeLa cells. C60′s ability to induce apoptosis of carcinoma cells after sonoexcitation with US provides a promising novel approach for cancer treatment.
Background and objective: Accurate and fast diagnosis of rheumatic diseases affecting the hands is essential for further treatment decisions. Fluorescence optical imaging (FOI) visualizes inflammation-induced impaired microcirculation by increasing signal intensity, resulting in different image features. This analysis aimed to find specific image features in FOI that might be important for accurately diagnosing different rheumatic diseases.
Patients and methods: FOI images of the hands of patients with different types of rheumatic diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and connective tissue diseases (CTD), were assessed in a reading of 20 different image features in three phases of the contrast agent dynamics, yielding 60 different features for each patient. The readings were analyzed for mutual differential diagnosis of the three diseases (One-vs-One) and each disease in all data (One-vs-Rest). In the first step, statistical tools and machine-learning-based methods were applied to reveal the importance rankings of the features, that is, to find features that contribute most to the model-based classification. In the second step machine learning with a stepwise increasing number of features was applied, sequentially adding at each step the most crucial remaining feature to extract a minimized subset that yields the highest diagnostic accuracy.
Results: In total, n = 605 FOI of both hands were analyzed (n = 235 with RA, n = 229 with OA, and n = 141 with CTD). All classification problems showed maximum accuracy with a reduced set of image features. For RA-vs.-OA, five features were needed for high accuracy. For RA-vs.-CTD ten, OA-vs.-CTD sixteen, RA-vs.-Rest five, OA-vs.-Rest eleven, and CTD-vs-Rest fifteen, features were needed, respectively. For all problems, the final importance ranking of the features with respect to the contrast agent dynamics was determined.
Conclusions: With the presented investigations, the set of features in FOI examinations relevant to the differential diagnosis of the selected rheumatic diseases could be remarkably reduced, providing helpful information for the physician.
The development of precision cancer medicine relies on novel formulation strategies for targeted drug delivery to increase the therapeutic outcome. Biocompatible polymer nanoparticles, namely dextran-graft-polyacrylamide (D-g-PAA) copolymers, represent one of the innovative non-invasive approaches for drug delivery applications in cancer therapy. In this study, the star-like D-g-PAA copolymer in anionic form (D-g-PAAan) was developed for pH-triggered targeted drug delivery of the common chemotherapeutic drugs – doxorubicin (Dox) and cisplatin (Cis). The initial D-g-PAA copolymer was synthesized by the radical graft polymerization method, and then alkaline-hydrolyzed to get this polymer in anionic form for further use for drug encapsulation. The acidification of the buffer promoted the release of loaded drugs. D-g-PAAan nanoparticles increased the toxic potential of the drugs against human and mouse lung carcinoma cells (A549 and LLC), but not against normal human lung cells (HEL299). The drug-loaded D-g-PAAan-nanoparticles promoted further oxidative stress and apoptosis induction in LLC cells. D-g-PAAan-nanoparticles improved Dox accumulation and drugs’ toxicity in a 3D LLC multi-cellular spheroid model. The data obtained indicate that the strategy of chemotherapeutic drug encapsulation within the branched D-g-PAAan nanoparticle allows not only to realize pH-triggered drug release but also to potentiate its cytotoxic, prooxidant and proapoptotic effects against lung carcinoma cells.
Label-free direct-optical biosensors such as surface-plasmon resonance (SPR) spectroscopy has become a gold standard in biochemical analytics in centralized laboratories. Biosensors based on photonic integrated circuits (PIC) are based on the same physical sensing mechanism: evanescent field sensing. PIC-based biosensors can play an important role in healthcare, especially for point-of-care diagnostics, if challenges for a transfer from research laboratory to industrial applications can be overcome. Research is at this threshold, which presents a great opportunity for innovative on-site analyses in the health and environmental sectors. A deeper understanding of the innovative PIC technology is possible by comparing it with the well-established SPR spectroscopy. In this work, we shortly introduce both technologies and reveal similarities and differences. Further, we review some latest advances and compare both technologies in terms of surface functionalization and sensor performance.
Knowledge of optical constants, i.e. refractive index n and extinction coefficient k, and light scattering properties of optical polymers are required to optimize micro-optics for light-emitting diodes in terms of efficiency, color properties and light distribution. We present here a model-based diagnostic approach to determine the optical properties of polymers, which should be particularly useful in the development of plastics for optical applications. Optical constants and scattering coefficients were obtained from transmission and reflection measurements in a wavelength range from UV to NIR taking into account scattering effects due to rough surfaces and volume inhomogeneity. Based on the models for the dielectric function, the molecular optical transition energies Eg, critical point energies, Urbach energies and exciton transition energies were determined. Rayleigh and Mie scattering model and van de Hulst's anomalous diffraction theory were applied to characterize scattering due to volume inhomogeneities. Scalar diffraction theory was applied to account for surface roughness scattering. Atomic force microscopy with nanomechanical characterization was used to characterize domains in size and shape and to assign optical scattering to a suitable morphological model. The combined optical and mechanical characterization help to improve the qualification of new polymer materials for optical applications.
Direct optical detection methods such as surface plasmon resonance imaging (SPRi) and photonic-integrated-circuits (PIC)-based biosensors provide a fast label-free detection of COVID-19 antibodies in real-time. Each technology, i.e., SPRi and PIC, has advantages and disadvantages in terms of throughput, miniaturization, multiplexing, system integration, and cost-effective mass production. However, both technologies share similarities in terms of sensing mechanism and both can be used as high-content diagnostics at or near to point of care, where the analyte is not just quantified but comprehensively characterized. This is significant because recent results suggest that not only the antibody concentration of the three isotypes IgM, IgG, and IgA but also the strength of binding (affinity) gives an indication of potential COVID-19 severity. COVID-19 patients with high titers of low affinity antibodies are associated with disease severity. In this perspective, we provide some insights into how SPR and PIC technologies can be effectively combined and complementarily used for a comprehensive COVID-19 severity monitoring. This opens a route toward an immediate therapy decision to provide patients a treatment in an early stage of the infection, which could drastically lowers the risk of a severe disease course.
Background
Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C60 fullerene (C60) at various molar ratios of the components, was explored against Lewis lung carcinoma (LLC).
Methods
C60–Ber noncovalent nanocomplexes were synthesized in 1:2, 1:1 and 2:1 molar ratios. Ber release from the nanocomplexes was studied after prolonged incubation at different pH with the liquid chromatography–mass spectrometry analysis of free Ber content. Biological effects of the free and C60-complaxated Ber were studied in vitro towards LLC cells with phase-contrast and fluorescence microscopy, flow cytometry, MTT reduction, caspase activity and wound closure assays. The treatment with C60–Ber nanocomplex was evaluated in vivo with the LLC-tumored C57Bl mice. The mice body weight, tumor size, tumor weight and tumor weight index were assessed for four groups, treated with saline, 15 mg C60/kg, 7.5 mg Ber/kg or 2:1 C60-Ber nanocomplex (15 mg C60/kg, 7.5 mg Ber/kg).
Results
Ber release from C60–Ber nanocomplexes was promoted with medium acidification. LLC cells treatment with C60–Ber nanocomplexes was followed by enhanced Ber intracellular uptake as compared to free Ber. The cytotoxicity of the studied agents followed the order: free Ber < 1:2 < 1:1 < 2:1 C60–Ber nanocomplex. The potency of cytotoxic effect of 2:1 C60–Ber nanocomplex was confirmed by 21.3-fold decrease of IC50 value (0.8 ± 0.3 µM) compared to IC50 for free Ber (17 ± 2 µM). C60–Ber nanocomplexes induced caspase 3/7 activation and suppressed the migration activity of LLC cells. The therapeutic potency of 2:1 C60–Ber nanocomplex was confirmed in a mouse model of LLC. The tumor growth in the group treated with 2:1 C60–Ber nanocomplex is suppressed by approximately 50% at the end of experiment, while in the tumor-bearing group treated with free Ber no therapeutic effect was detected.
Conclusions
This study indicates that complexation of natural alkaloid Ber with C60 may be a novel therapeutic strategy against lung carcinoma.
A combination of acrylate formulations and SiO2 nanoparticles is investigated with the aim to improve the optical properties of low-refractive index polymers that are used for the fabrication of planar optical waveguides. A decrease in refractive index and also in the thermo-optic coefficient of nanocomposite materials is clearly demonstrated, while some formulations exhibit an increase in the glass transition temperature. The possibility of using these nanocomposite materials to fabricate waveguiding layers with low optical propagation losses at telecommunication wavelengths around 1550 nm is also shown. The nanomaterials can be applied in optical microchips on polymer platforms.