Targosomes: Anti-HER2 PLGA nanocarriers for bioimaging, chemotherapy and local photothermal treatment of tumors and remote metastases.

Developing combined cancer therapy strategies is of utmost importance as it can enhance treatment efficacy, overcome drug resistance, and ultimately improve patient outcomes by targeting multiple pathways and mechanisms involved in cancer growth and progression. Specifically, the potential of developing a combination chemo&photothermal therapy using targeted polymer nanoparticles as nanocarriers offers a promising approach for synergistic cancer treatment by combining the benefits of both therapies, such as targeted drug delivery and localized hyperthermia. Here, we report the first targeted anti-HER2 PLGA nanocarriers, called targosomes, that simultaneously possess photothermal, chemotherapeutic and diagnostic properties using only molecular payloads. Biocompatible poly(lactic-co-glycolic acid), PLGA, nanoparticles were loaded with photosensitizer phthalocyanine, diagnostic dye Nile Blue, and chemotherapeutic drug irinotecan, which was chosen as a result of screening a panel of theragnostic nanoparticles. The targeted delivery to cell surface oncomarker HER2 was ensured by nanoparticle modification with the anti-HER2 monoclonal antibody, trastuzumab, using the one-pot synthesis method without chemical conjugation. The irradiation tests revealed prominent photothermal properties of nanoparticles, namely heating by 35 °C in 10 min. Nanoparticles exhibited a 7-fold increase in binding and nearly an 18-fold increase in cytotoxicity for HER2-overexpressing cells compared to cells lacking HER2 expression. This enhancement of cytotoxicity was further amplified by >20-fold under NIR light irradiation. In vivo studies proved the efficacy of nanoparticles for bioimaging of primary tumor and metastasis sites and demonstrated 93% tumor growth inhibition, making these nanoparticles excellent candidates for translation into theragnostic applications.

Multiple and spectrally robust photonic magic angles in reconfigurable α-MoO3 trilayers.

The emergence of a topological transition of the polaritonic dispersion in twisted bilayers of anisotropic van der Waals materials at a given twist angle-the photonic magic angle-results in the diffractionless propagation of polaritons with deep-subwavelength resolution. This type of propagation, generally referred to as canalization, holds promise for the control of light at the nanoscale. However, the existence of a single photonic magic angle hinders such control since the canalization direction in twisted bilayers is unique and fixed for each incident frequency. Here we overcome this limitation by demonstrating multiple spectrally robust photonic magic angles in reconfigurable twisted α-phase molybdenum trioxide (α-MoO3) trilayers. We show that canalization of polaritons can be programmed at will along any desired in-plane direction in a single device with broad spectral ranges. These findings open the door for nanophotonics applications where on-demand control is crucial, such as thermal management, nanoimaging or entanglement of quantum emitters.

Hexagonal boron nitride nanophotonics: a record-breaking material for the ultraviolet and visible spectral ranges.

A global trend towards miniaturization and multiwavelength performance of nanophotonic devices drives research on novel phenomena, such as bound states in the continuum and Mietronics, as well as surveys for high-refractive index and strongly anisotropic materials and metasurfaces. Hexagonal boron nitride (hBN) is one of the promising materials for future nanophotonics owing to its inherent anisotropy and prospects of high-quality monocrystal growth with an atomically flat surface. Here, we present highly accurate optical constants of hBN in the broad wavelength range of 250-1700 nm combining imaging ellipsometry measurements, scanning near-field optical microscopy and first-principles quantum mechanical computations. hBN's high refractive index, up to 2.75 in the ultraviolet (UV) and visible range, broadband birefringence of ∼0.7, and negligible optical losses make it an outstanding material for UV and visible range photonics. Based on our measurement results, we propose and design novel optical elements: handedness-preserving mirrors and subwavelength waveguides with dimensions of 40 nm operating in the visible and UV ranges, respectively. Remarkably, our results offer a unique opportunity to bridge the size gap between photonics and electronics.

Twist-tunable polaritonic nanoresonators in a van der Waals crystal.

Optical nanoresonators are key building blocks in various nanotechnological applications (e.g., spectroscopy) due to their ability to effectively confine light at the nanoscale. Recently, nanoresonators based on phonon polaritons (PhPs)-light coupled to lattice vibrations-in polar crystals (e.g., SiC, or h-BN) have attracted much attention due to their strong field confinement, high quality factors, and their potential to enhance the photonic density of states at mid-infrared (mid-IR) frequencies, where numerous molecular vibrations reside. Here, we introduce a new class of mid-IR nanoresonators that not only exhibit the extraordinary properties previously reported, but also incorporate a new degree of freedom: twist tuning, i.e., the possibility of controlling their spectral response by simply rotating the constituent material. To achieve this result, we place a pristine slab of the van der Waals (vdW) α-MoO3 crystal, which supports in-plane hyperbolic PhPs, on an array of metallic ribbons. This sample design based on electromagnetic engineering, not only allows the definition of α-MoO3 nanoresonators with low losses (quality factors, Q, up to 200), but also enables a broad spectral tuning of the polaritonic resonances (up to 32 cm-1, i.e., up to ~6 times their full width at half maximum, FWHM ~5 cm-1) by a simple in-plane rotation of the same slab (from 0 to 45°). These results open the door to the development of tunable and low-loss IR nanotechnologies, fundamental requirements for their implementation in molecular sensing, emission or photodetection applications.

Planar refraction and lensing of highly confined polaritons in anisotropic media.

Refraction between isotropic media is characterized by light bending towards the normal to the boundary when passing from a low- to a high-refractive-index medium. However, refraction between anisotropic media is a more exotic phenomenon which remains barely investigated, particularly at the nanoscale. Here, we visualize and comprehensively study the general case of refraction of electromagnetic waves between two strongly anisotropic (hyperbolic) media, and we do it with the use of nanoscale-confined polaritons in a natural medium: α-MoO3. The refracted polaritons exhibit non-intuitive directions of propagation as they traverse planar nanoprisms, enabling to unveil an exotic optical effect: bending-free refraction. Furthermore, we develop an in-plane refractive hyperlens, yielding foci as small as λp/6, being λp the polariton wavelength (λ0/50 compared to the wavelength of free-space light). Our results set the grounds for planar nano-optics in strongly anisotropic media, with potential for effective control of the flow of energy at the nanoscale.

Enabling propagation of anisotropic polaritons along forbidden directions via a topological transition.

Polaritons with directional in-plane propagation and ultralow losses in van der Waals (vdW) crystals promise unprecedented manipulation of light at the nanoscale. However, these polaritons present a crucial limitation: their directional propagation is intrinsically determined by the crystal structure of the host material, imposing forbidden directions of propagation. Here, we demonstrate that directional polaritons (in-plane hyperbolic phonon polaritons) in a vdW crystal (α-phase molybdenum trioxide) can be directed along forbidden directions by inducing an optical topological transition, which emerges when the slab is placed on a substrate with a given negative permittivity (4H-silicon carbide). By visualizing the transition in real space, we observe exotic polaritonic states between mutually orthogonal hyperbolic regimes, which unveil the topological origin of the transition: a gap opening in the dispersion. This work provides insights into optical topological transitions in vdW crystals, which introduce a route to direct light at the nanoscale.

Giant optical anisotropy in transition metal dichalcogenides for next-generation photonics.

Large optical anisotropy observed in a broad spectral range is of paramount importance for efficient light manipulation in countless devices. Although a giant anisotropy has been recently observed in the mid-infrared wavelength range, for visible and near-infrared spectral intervals, the problem remains acute with the highest reported birefringence values of 0.8 in BaTiS3 and h-BN crystals. This issue inspired an intensive search for giant optical anisotropy among natural and artificial materials. Here, we demonstrate that layered transition metal dichalcogenides (TMDCs) provide an answer to this quest owing to their fundamental differences between intralayer strong covalent bonding and weak interlayer van der Waals interaction. To do this, we made correlative far- and near-field characterizations validated by first-principle calculations that reveal a huge birefringence of 1.5 in the infrared and 3 in the visible light for MoS2. Our findings demonstrate that this remarkable anisotropy allows for tackling the diffraction limit enabling an avenue for on-chip next-generation photonics.

[Dilated cardiomyopathy in patients with schizophrenia].

AIM: To study the frequency of pathoanatomic and some clinical signs of dilated cardiomyopathy (DCM) in schizophrenic patients (SPs). SUBJECTS AND METHODS: Autopsy records were studied in 838 SPs treated at a psychiatric hospital in 1952 to 2007. The records were used to select DCM cases (n = 74) and sudden deaths (n = 101) and to examine 339 electrocardiograms (ECG). The 2006-2007 information obtained in the dissecting rooms of three Tver hospitals (1413 sections) was analyzed. RESULTS: DCM was absent (neuroleptics were not used) before 1956. With the application of neuroleptics, the diagnosis of DCM cases significantly increased and its rate was 14.2% among the dead SPs. DCM might be a cause of sudden death in 21.8% of SPs. The rate of pathological ECG signs noticeably increased with the longer use of neuroleptics. In the hospital-wide network, the detection rate for DCM was 0.5% of the autopsies. CONCLUSION: The use of neuroleptics, in SPs in particular, may lead to the development of DCM.

[Consumption of table salt and psychological status in patients with arterial hypertension].

The frequency of neurotic disorder was studied in 630 patients with arterial hypertension (AH) who consumed large amounts of table salt (TS). Their threshold gustatory sensitivity to salt (TGS) was determined in conjunction with daily sodium excretion in urine and psychological features (using the SMOL test. MOS SF-36 questionnaire, and Zung depression scale). It was shown that AH patients consume 6-7 g more salt than healthy subjects due to the love of salty food and high TGS. Such patients are characterized by high activity and ambitiousness, and unrealized strive for obtaining a higher position. Their psychological status is dominated by anxiety, tension, and depression. The state of the vegetative nervous system is prevailed by sympaticotony.

[Endoscopical methods in the differential diagnosis of tuberculosis and cancer of the respiratory system].

For 25 years (1986-2011) in endoscopy unit of the branch of the 1 FBU "3 TSVKG Russian Ministry of Defense n. a. A.A. Vishnevskiy--" initially examined 18 169 patients admitted on the various forms of pulmonary tuberculosis. In the bronchial study tuberculosis of bronchus was diagnosed in 1544 patients, representing 8.5% of all TB patients. Complicated bronchial tuberculosis (infiltrative-ulcerative and broncho-fistulezny TB) were diagnosed in 382 (24.8%) patients. Neoplastic process in bronchi was detected in 145 (0.8%) patients, including the central cancer was found in 109, peripheral--at 36. An increase in tuberculosis and cancer of the respiratory system requires medical endoscopists to targeted search for endoscopic studies, not only the specific features of tuberculous bronchial lesions, but also the cancer process in them. In the case of detection of pathological changes in the pleura and lung parenchyma should be preferred thoracoscopy.

[Characteristics of duodenogastric reflux in duodenal ulcer patients and its dynamics after Helicobacter pylori eradication].

UNLABELLED: Studying role of duodenogastric reflux (DGR) in pathogenesis and sanogenesis of duodenal ulcer (DU). MATERIAL AND METHODS: 233 DU patients (92 patients with a mild, 45--with modern and 96--with the complicated current of disease) are surveyed. Control group were 100 healthy volunteers. Clinical research, endoscopy and 24-hours pH-metria was carried out. In a year after eradication Helicobacter pylori (Hp) 30 patients are repeatedly surveyed. RESULTS: at healthy acidity more low, and DGR above and more for a long time, than at DU patients. DU was especially supressed at complicated current DU. Eradication Hp was accompanied by acidity normalization only at mild DU, and at complicated DU--is not present. CONCLUSION: at healthy people DGR arises in reply to antrum's acidification and has compensative value, and at DU there is the considerable suppression leading to insufficiency of antrum's alkalization. After eradication Hp normalization DGR is marked only at mild current DU.

[Syndrome of hypovolemia in patients with arterial hypertension].

A total of 440 patients with essential arterial hypertension underwent measurement of daily sodium excretion in urine followed by calculation of table salt consumption, 24-hour monitoring of AP and determination of daily AP index. Patients divided into 3 groups of n = 98, 120 and 222 were estimated to daily consume 9, 12 and 16 or more gram of salt respectively. Clinical manifestations of arterial hypertension and AP values progressively increased from group 1 to 3. These changes were paralleled by increased requirement of hypotensive agents, AP variations, and the number of non-dippers and night-pickers. It is concluded that the above features of AH correlate with salt consumption and are related to hypervolemia.

[Psychological status of hypertensive patients consuming higher amounts of table salt].

AIM: To estimate a possible relationship of neurotic personality disorders to increased dietary salt intake. SUBJECTS AND METHODS: Two hundred and thirty patients with essential hypertension were examined. Salt taste sensitivity threshold and daily urinary sodium excretion were determined; the psychological status of the patients was rated by the Mini-Mental State Examination questionnaire; their attitude towards to disease was assessed by the Bekhterev Institute personality questionnaire, the severity of depression was evaluated by the Beck depression inventory. RESULTS: The hypertensive patients consuming excessive amounts of salt have been ascertained to complain of cardiovascular and neurotic disorders more frequently; their disease is accompanied by frequently evolving hypertensive crises. Anxiety and tension are prevalent in their psychological status. Almost 50% of the patients have depression. A harmonious disease attitude is seen in only a third of cases whereas the neurasthenic and anxious types play a dominant role. CONCLUSION: The patients taking higher salt amounts are observed to seek medical advice on the one hand and to show a predominance of neurasthenic and anxious disease attitudes with a tendency towards incompliance on the other. The findings show it necessary to notify hypertensive patients during their examination and management.

[Functional state of arterioles in patients with essential hypertension and arterial hypertension developed at the background of diabetes mellitus].

With the aim of studying linear velocity characteristics of arteriolar blood flow and reactivity of arterioles we examined 80 patients with essential arterial hypertension (AH), 83 patients with type 2 diabetes mellitus (DM) with concomitant AH, and 63 healthy people. In all patients examination included ultrasound continuous wave dopplerography of microcirculatory vascular bed at rest and after distant warming test. It was found that in patients with essential AH blood flow velocity in arterioles was maximal, increment of arteriolar blood flow in response to warming was lower than in healthy persons. In patients with type 2 DM minimal linear velocity characteristics of arteriolar blood flow and its increment in response to warming test were minimal. Results of the study evidence for principal differences of functioning and reactivity of arterioles in patients with essential AH and AH developed at the background of diabetes mellitus.

[What contributes to the transformation of Helicobacter pylori from symbiont into the etiopathogenetical factor of duodenal ulcer?].

UNLABELLED: The aim was to study the relationship duodenogastral reflux (DGR) and Helicobacterpylori infection (Hp) at duodenal ulcer (DU). MATERIAL AND METHODS: Group 1-50 patients with uncomplicated course of DU, Group 2-75 patients with destructive complications of DU; Group 3-40 "healthy" volunteers. It was performed daily EGDS, pH meter, semi-quantitative assessment of contamination of the Hp. RESULTS: The acidity in the body of the stomach was highest in group 2, and lowest--in group 3, patients diagnosed DU night rush giperatsidnosti. In the night period patients from the 1st and 3rd groups were recorded an increase of antral pH, including the expense of growth duration of DGR, while in group 2 reflux was extremely short. The maximum Hp dissemination was in a bulb at fetomaternal of DU. CONCLUSIONS: in healthy individuals DGR intragastral involved in the regulation of pH, in patients with uncomplicated DU while reducing the duration of this resonance persists compensation of antral alkalization, and complications throughout the DGR sharply depressed, which is accompanied by severe decompensation alkalization of antrum. Bulbs semination with Hp inversely proportional to the intensity of this resonance.

[Impaired gustatory sensitivity of the tongue to table salt as a risk factor of arterial hypertension].

The study included 630 patients with verified diagnosis of arterial hypertension (AH) in whom 24 hr AP monitoring was performed, threshold gustatory sensitivity of the tongue to table salt (TGS) measured, and habit to add salt to the cooked food evaluated. Measurement of Na in daily urine of 442 patients was followed by estimation of salt consumption. The results were compared with those obtained in 100 patients with newly diagnosed AH. The control group comprised 288 subjects. TGS in AH patients was significantly higher than in controls and directly related to clinical features of the disease, high AP values, age, smoking habits, hypercholesterolemia, abdominal-type obesity, and hereditary predisposition. TGS positively correlated with daily urinary excretion of NaCl (r = 0.4-0.7; p < 0.05-0.01). High TGS decreased under effect of hypotensive therapy.

[Arteriolar circulation and arterial pressure in patients with essential hypertension].

Arteriolar circulation and its relationship with arterial pressure were studied in 127 patients with essential hypertension and 63 healthy subjects using continuous US dopplerography of the microcirculatory system at rest. Linear arteriolar blood flow rate was measured in healthy subjects and 47 patients before and after primary indapamide therapy. It was found to equal 17.7 (mean 9.1) cm/s in systole and 8.7 cm/s in diastole in the patients versus 12.2 (7.3) and 4.3 respectively in the healthy subjects (p = 0.005) giving indirect evidence of narrowed diameter of arterioles. Arteriolar circulation was shown to depend on the duration of arterial hypertension. Both AP and linear arteriolar blood flow rate decreased under effect of hypotensive therapy but there was no significant correlation between the two parameters.