Recent progress in the detection and treatment of atherosclerosis by nanoparticles

Cardiovascular diseases (CVDs) have high mortality and morbidity in the US and presently rank as one of the leading causes of death. Atherosclerosis (AS) acts as one of the CVDs, playing an important role in mortality because of many lethal complications. The common cause of AS is that low-density lipoprotein (LDL) in the blood circulation enters the intima through endothelial cells that have been broken for various reasons. Under the action of inflammatory factors secreted by damaged endothelial cells, monocytes also enter the inner membrane and differentiate into macrophages. Macrophages engulf the oxidized LDL and become foam cells which eventually become apoptotic. However, recent studies have shown that LDL entry into the intima, an important step in AS, may be associated with endothelial cells actively inhaling LDL through the receptor. Nanotechnology is a promising technology that can be applied in the noninvasive imaging and therapy of AS. Nanoparticles (NPs) have the ability to passively target AS because of their inherent small diameter. They can also be loaded with chemicals for targeting lesions, contrast agents for imaging, and drugs for treatment to achieve accurate diagnosis and treatment of AS. This review consequently highlights the recent progress in the detection and treatment of AS by NPs.     

Formulation of Tioconazole and Melaleuca alternifolia Essential Oil Pickering Emulsions for Onychomycosis Topical Treatment

Onychomycosis is a disease that affects many adults, whose treatment includes both oral and topical therapies with low cure rates. The topical therapy is less effective but causes fewer side effects. This is why the development of an effective, easy to apply formulation for topical treatment is of high importance. We have used a nanotechnological approach to formulate Pickering emulsions (PEs) with well-defined properties to achieve site-specific delivery for antifungal drug combination of tioconazole and Melaleuca alternifolia essential oil. Silica nanoparticles with tailored size and partially hydrophobic surface have been synthesized and used for the stabilization of PEs. In vitro diffusion studies have been performed to evaluate the drug delivery properties of PEs. Ethanolic solution (ES) and conventional emulsions (CE) have been used as reference drug formulations. The examination of the antifungal effect of PEs has been performed on Candida albicans and Trichophyton rubrum as main pathogens. In vitro microbiological experimental results suggest that PEs are better candidates for onychomycosis topical treatment than CE or ES of the examined drugs. The used drugs have shown a significant synergistic effect, and the combination with an effective drug delivery system can result in a promising drug form for the topical treatment of onychomycosis.     

Ab initio and coupled-perturbed density functional theory estimation of zero-field splittings in MnII transition metal complexes

The paper presents a method comparison for the prediction of zero-field splitting (ZFS) parameters in a series of Mn (II) coordination complexes. The test set consists of Mn (II) complexes that are experimentally well-characterized by X-ray diffraction and high-field electron paramagnetic resonance. Their ZFS parameters have been calculated using density functional theory (DFT) as well as complete active space self-consistent field (CASSCF) methods. It is shown that the recently introduced coupled-perturbed spin-orbit coupling (CP-SOC) approach [ Neese, F. J. Chem. Phys. 2007, 127, 164112 ] together with hybrid-DFT functionals leads to a slope of the correlation line (plot of experimental vs calculated D values) that is essentially unity provided that the direct spin-spin interaction is properly included in the treatment. This is different from our previous DFT study on the same series of complexes where a severe overestimation of the D parameter has been found [ Zein, S. ; Duboc, C. ; Lubitz, W. ; Neese, F. Inorg. Chem. 2008, 47, 134 ]. CASSCF methods have been used to evaluate the ZFS in an "ab initio ligand-field" type treatment. The study demonstrates that a substantial part of the relevant physics is lost in such a treatment since only excitations within the manganese d-manifold are accounted for. Thus, a severe underestimation of the D parameter has been found. Because the CASSCF calculations in combination with quasidegenerate perturbation theory treats the SOC to all orders, we have nevertheless verified that second-order perturbation theory is an adequate approximation in the case of the high-spin d (5) configuration.     

Enhanced adhesion of copper plating to polyether ether ketone based on active oxygen species generated under ultraviolet irradiation

Polyether ether ketone (PEEK) is a substrate for metal plating to overcome insulation defects and satisfy the increased demands of mechanically robust electronic circuit boards. However, pristine PEEK is hydrophobic; hence, the adhesion between the metal film and PEEK substrate is poor. Therefore, the PEEK surface should be modified to improve hydrophobicity. We have proposed the active oxygen (AOS) treatment under ultraviolet (UV) light as an alternative to a conventional plasma treatment method. Characteristics of the PEEK surfaces obtained by these methods are compared. We explore the effects of reactive-oxygen and UV light exposure time on the PEEK surface modification. The contact angle of water drop on PEEK after the AOS treatment is lower than that of untreated PEEK. Furthermore, COO groups are observed on the PEEK surface after the treatment. Although plasma treatment has the effect of roughening the surface, it is desirable not to roughen the surface for use in electronic circuit boards. Moreover, we have reported the adhesion strength between PEEK and copper plating without surface roughening.     

Thermally induced phase separation of polystyrene-poly(vinyl methyl ether) mixtures

Past differential scanning calorimetry and dielectric relaxation measurements have established that polystyrene (PS)-poly(vinyl methyl ether) (PVME) mixtures exhibit a degree of compatibility when cast from toluene, whereas they are incompatible when cast from chloroform or trichloroethylene. The present study reports that toluene-cast mixtures can be phase-separated by thermal treatment at temperatures exceeding 125°C. This is true for samples containing 20–80 wt-% PS. The temperature of phase separation varies with heating rate; isothermal heating times needed to cause phase separation increase rapidly as the temperature approaches 125°C. Reversibility of the phase separation process depends upon such factors as cooling rate, annealing time, treatment temperature, and thermal history. By annealing and/or slow cooling, all thermally phase-separated mixtures have been brought back to their original state of compatibility. That is, there is no evidence for true irreversiblity of phase separation in thermally treated samples. Quench-cooled samples remain phase-separated indefinitely at room temperature, but this is attributed to rapid cooling below the glass transition of the PS. Chloroform-cast and trichloroethylene-cast mixtures have not been brought to a compatible state by thermal treatment, even after lengthy annealing and slow cooling steps.     

新型高硅Y(NHSY)沸石的研究:Ⅱ.NHSY沸石的结构特点

用ＩＲ，ＸＰＳ，ＴＥＭ，低温氮吸附和化学分析等手段表征了ＮＨＳＹ沸石的结构特点，结果表明，ＮＨＳＹ具有Ａｌ分布均匀，骨架Ａｌ空位少、含非骨架Ａｌ少而适量和二次孔体系发达等显著特点，这些特点使ＮＨＳＹ具有很好的结构稳定性和很高的催化活性及选择性。     

Nanotexturing of polystyrene surface in fluorocarbon plasmas: from sticky to slippery superhydrophobicity

In this work plasma etching processes have been studied to roughen and fluorinate polystyrene surface as an easy method to achieve a superhydrophobic slippery character. Radiofrequency discharges have been fed with CF(4)/O(2) mixtures and the effect of the O(2):CF(4) ratio, the input power, and the treatment duration have been investigated in terms of wettability, with focus on sliding performances. For this purpose, surface morphological variations, evaluated by means of scanning electron microscopy and atomic force microscopy, together with the chemical assessment by X-ray photoelectron spectroscopy, have been correlated with water contact angle hysteresis and volume resolved sliding angle measurements. Results indicate that by increasing the height and decreasing the density of the structures formed by etching, within a tailored range, a transition from sticky to slippery superhydrophobicity occurs. A short treatment time (5 min) is sufficient to obtain such an effect, provided that a high power input is utilized. Optimized surfaces show a unaltered transparency to visible light according to the low roughness produced.     

Electrochemical modification of surface morphology of Au/Ti bilayer films deposited on a Si prism for in situ surface-enhanced infrared absorption (SEIRA) spectroscopy

Surface-enhanced infrared absorption (SEIRA)-active Au/Ti bilayer films sputter deposited on Si substrates have been prepared by an electrochemical annealing (ECA) treatment for the first time. The application of Au/Ti bilayer films on Si substrates to the spectroscopic technique is a promising alternative to the conventional technique using directly deposited Au films on Si substrates, offering excellent adhesive durability of the deposited metal films. However, Au/Ti bilayer films have never been selected for the spectroscopy technique because the films in the as-prepared state exhibit relatively smooth surface morphology: the excitation of the localized surface plasmon is vital to achieving SEIRA enhancements but could hardly be observed on the smooth morphology. It is shown by ex situ scanning tunneling microscopy measurements that the unfavorable smooth morphology of the as-prepared Au/Ti bilayer films can be modified by the ECA treatment to a reasonably rough, island-structure morphology similar to that of the conventional SEIRA-active Au films. In situ infrared absorption spectroscopy of adsorbed sulfate anions has been conducted on the Au/Ti bilayer film both before and after ECA treatment. The spectroscopy measurements demonstrate that the SEIRA activity of the film after being subjected to the treatment is significantly improved so that the technique could detect adsorbates on the film electrodes even with the submonolayer coverage. As an additional benefit, the ECA treatment has brought about a substantial increase in the fraction of Au(111) domains on the polycrystalline Au film surfaces. Accordingly, this approach enables us to prepare SEIRA-active Au films having sufficient adhesion to the Si substrates as well as the highly preferred (111) orientation.     

Neuroprotective Activities of Crossyne flava Bulbs and Amaryllidaceae Alkaloids: Implications for Parkinson’s Disease

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and affects approximately 6.3 million people worldwide. To date, the treatment of PD remains a challenge, as available treatment options are known to be associated with serious side effects; hence, the search for new treatment strategies is critical. Extracts from the Amaryllidaceae plant family as well as their alkaloids have been reported to have neuroprotective potentials. This study, therefore, investigated the biological activities of Crossyne flava and its isolated alkaloids in an in vitro MPP⁺ (1-methyl-4-phenylpyridinium) PD model using SH-SY5Y cells. The effects of the total extract as well as the four compounds isolated from Crossyne flava (i.e., pancratinine B (1), bufanidrine (2), buphanisine (3), and epibuphanisine (4)) were evaluated for cell viability, neuroprotection, levels of reactive oxygen species (ROS), adenosine triphosphate activity (ATP), and caspase 3/7 activity in SH-SY5Y cells. The results obtained showed that pre-treatment with both the extract and the isolated compounds was effective in protecting the SH-SY5Y cells from MPP⁺-induced neurotoxicity and inhibited ROS generation, ATP depletion as well as apoptosis induction in the SH-SY5Y cells. The results of this study show that the Amaryllidaceae plant family may be a source of novel compounds for the treatment of neurodegenerative diseases, which validates the reported traditional uses.     

Recent Progress on Biological Activity of Amaryllidaceae and Further Isoquinoline Alkaloids in Connection with Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disease recognized as the most common form of dementia among elderly people. Due to the fact that the exact pathogenesis of AD still remains to be fully elucidated, the treatment is only symptomatic and available drugs are not able to modify AD progression. Considering the increase in life expectancy worldwide, AD rates are predicted to increase enormously, and thus the search for new AD drugs is urgently needed. Due to their complex nitrogen-containing structures, alkaloids are considered to be promising candidates for use in the treatment of AD. Since the introduction of galanthamine as an antidementia drug in 2001, Amaryllidaceae alkaloids (AAs) and further isoquinoline alkaloids (IAs) have been one of the most studied groups of alkaloids. In the last few years, several compounds of new structure types have been isolated and evaluated for their biological activity connected with AD. The present review aims to comprehensively summarize recent progress on AAs and IAs since 2010 up to June 2021 as potential drugs for the treatment of AD.     

Rhodium Nanoparticles as a Novel Photosensitizing Agent in Photodynamic Therapy against Cancer

Photodynamic therapy (PDT) is a promising alternative treatment for different types of cancer due to its high selectivity, which prevents healthy tissues from being damaged. The use of nanomaterials in PDT has several advantages over classical photosensitizing agents, due to their unique properties and their capacity for functionalization. Especially interesting is the use of metallic nanoparticles, which are capable of absorbing electromagnetic radiation and either transferring this energy to oxygen molecules for the generation of reactive oxygen species (ROS) or dissipating it as heat. Although previous reports have demonstrated the capacity of Rh derivatives to serve as anti-tumor drugs, to the best of our knowledge there have been no studies on the potential use of small-sized Rh nanoparticles as photosensitizers in PDT. In this study, 5 nm Rh nanoparticles have been synthesized and their potential in PDT has been evaluated. The results show that treatment with Rh nanoparticles followed by NIR irradiation induces apoptosis in cancer cells through a p53-independent mechanism.     

聚金属氧酸盐在阿尔兹海默症治疗中的新进展

从聚金属氧酸盐(POMs)对β-淀粉样蛋白(Aβ)聚集的调控作用、 水解及光动力治疗等方面介绍其在阿尔兹海默症(AD)治疗中的最新研究进展, 为进一步研究POMs抗AD药物活性提供了参考.     

Autocatalytic polymerization of selenium/polypyrrole nanocomposites as functional theranostic agents for multi-spectral photoacoustic imaging and photothermal therapy of tumor

The synchronization of diagnosis and treatment is a new trend in cancer treatment. Photoacoustic imaging (PAI) and photothermal therapy (PTT) are recognized as one of the perfect combinations. The autocatalytic polymerization of selenium/polypyrrole (Se@PPy) nanocomposites with a wide-absorption band at near-infrared region (NIR, 800 nm) has been developed in this paper. The wide optical absorption characteristics enable Se@PPy nanocomposites to achieve multi-spectral PAI. Ex vivo experiments show desirable photoacoustic ability of the Se@PPy nanocomposites at wavelengths ranging from 700 nm to 900 nm, which is better than that of commercial indocyanine green (ICG). Se@PPy nanocomposites have high photothermal conversion efficiency up to 36.3% as well as excellent photo-thermal stability. In vitro cytotoxicity test demonstrates that the Se@PPy nanocomposites have good bio-safety. Furthermore, the feasibility of Se@PPy nanocomposites for enhancing multi-spectral PAI guided PTT was verified on 4T1 tumor-bearing nude mice. Our results indicate that Se@PPy nanocomposites could be used as an effective theranostic agent for near-infrared light-mediated PAI and PTT of tumor.     

Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy

We review drug conjugates combining a tumor-selective moiety with a cytotoxic agent as cancer treatments. Currently, antibody-drug conjugates (ADCs) are the most common drug conjugates used clinically as cancer treatments. While providing both efficacy and favorable tolerability, ADCs have limitations due to their size and complexity. Peptides as tumor-targeting carriers in peptide-drug conjugates (PDCs) offer a number of benefits. Melphalan flufenamide (melflufen) is a highly lipophilic PDC that takes a novel approach by utilizing increased aminopeptidase activity to selectively increase the release and concentration of cytotoxic alkylating agents inside tumor cells. The only other PDC approved currently for clinical use is ¹⁷⁷Lu-dotatate, a targeted form of radiotherapy combining a somatostatin analog with a radionuclide. It is approved as a treatment for gastroenteropancreatic neuroendocrine tumors. Results with other PDCs combining synthetic analogs of natural peptide ligands with cytotoxic agents have been mixed. The field of drug conjugates as drug delivery systems for the treatment of cancer continues to advance with the application of new technologies. Melflufen provides a paradigm for rational PDC design, with a targeted mechanism of action and the potential for deepening responses to treatment, maintaining remissions, and eradicating therapy-resistant stem cells.     

A study of cryostructuring of polymer systems. 45. Effect of porosity of dispersed filler on physicochemical characteristics of composite poly(vinyl alcohol) cryogels

Composite cryogels simulating the properties of waterproof screens of hydraulic structures, such as protruding dykes and dams, have been obtained by a cryogenic treatment (freezing at –10…–30°C followed by incubation in the frozen state for 12 h and defrosting at a rate of 0.03°C/min) of suspensions of calcium-carbonate-containing (marble or coquina) or cellulose-containing (microcrystalline cellulose or sawdust) particles in aqueous poly(vinyl alcohol) solutions. Viscometric examinations of initial suspensions have shown that adhesion contacts arise between filler particles, as well as discrete and continuous phases, already at the stage of suspension preparation, thereby affecting the properties of resulting cryogels. This is most pronounced when high-porosity sawdust is used as a filler. It has been shown that all the dispersed materials used in the work are “active” fillers for poly(vinyl alcohol) cryogels, these fillers increasing the rigidity of the formed composites. Therewith, porous particles, into which the polymer solution can penetrate, are more efficient. The dependence of the composite rigidity on the temperature of the cryogenic treatment has, as a rule, a bell-shaped pattern with a maximum in the region of –20°C. Being tested for water permeability, the obtained model composite cryogels have exhibited pronounced antifiltration properties (the filtration coefficient is ≤(1–2) × 10^–9 cm/s), thus indicating that such materials are promising for solving problems relevant to the protection of fascine hydraulic structures from erosion with snow water.     

CLINICAL LASER PHOTODYNAMIC THERAPY IN THE TREATMENT OF BLADDER CARCINOMA

Abstract The treatment of bladder carcinoma using dihematoporphyrin ether (DHE) and laser photodynamic therapy (PDT) is described herein. Patients selected for this study have cytology- and biopsy-proven transitional cell carcinoma, no histologic evidence of muscle invasion, and negative excretory urograms. Sixteen patients have been treated, with follow-up from 6 to 36 months. Eleven have had a complete response, and 3 a partial response in that they required re-treatment for recurrence. Two of these patients have not recurred at this time. One of the patients who recurred had tumor extension into the prostatic urethra and has been successfully re-treated (disease-free at 6 months). There was one treatment failure and 1 patient lost to follow-up. Photosensitivity for up to 4 weeks is a known side-effect, but unexpected morbidity included a transient but significant increase in urinary frequency, urgency, and occasionally hematuria which spontaneously resolved within 3-4 weeks. Careful placement of the fiberoptic tip in the centre of the bladder, bladder distension during treatment with saline rather than water, the instillation of the minimum volume required to “smooth out” the mucosa for complete bladder photoradiation, and delivered energy of 25 J cm’or less may have prevented the more severe complications (i.e. bladder shrinkage) reported by Dougherty and Nseyo (personal communication). We also feel that there is some early evidence that a heightened immune response (similar to intravesical BCG) may potentially play some role in explaining the efficacy of PDT in long disease-free intervals, although this is just a histologic observation at present. It appears the PDT offers another practical treatment modality for non-invasive transitional cell carcinoma in patients refractory to standard surgical and chemotherapeutic regimens, and has been addressed by numerous other investigators such as Benson (1985) and Hisazumi (1983). We are presently recommending to our patients in these categories to undergo a course of PDT prior to relinquishing to cystectomy.