15 research outputs found
Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
Robust magnetism against pressure in non-superconducting samples prepared from lutetium foil and H2/N2 gas mixture
Recently, the claim of "near-ambient superconductivity" in a N-doped lutetium
hydride attracted enormous following-up investigations in the community of
condensed matter physics and material sciences. But quite soon, the
experimental results from different groups indicate consistently that no
evidence of near-ambient superconductivity is found in the samples synthesized
by the same method as the reported one, or by the other alternative methods.
From our extended high-pressure heat capacity and magnetic susceptibility
measurements on the samples prepared with the lutetium foil and H2/N2 gas
mixture, we report the finding of a magnetic transition at the temperature
about 56 K. Our results show that this magnetic phase is robust against
pressure up to 4.3 GPa, which covers the critical pressure of boosting the
claimed near room temperature superconductivity.Comment: 14 pages, 4 figure
Pressure-stabilized divalent ozonide CaO3 and its impact on Earth's oxygen cycles.
High pressure can drastically alter chemical bonding and produce exotic compounds that defy conventional wisdom. Especially significant are compounds pertaining to oxygen cycles inside Earth, which hold key to understanding major geological events that impact the environment essential to life on Earth. Here we report the discovery of pressure-stabilized divalent ozonide CaO3 crystal that exhibits intriguing bonding and oxidation states with profound geological implications. Our computational study identifies a crystalline phase of CaO3 by reaction of CaO and O2 at high pressure and high temperature conditions; ensuing experiments synthesize this rare compound under compression in a diamond anvil cell with laser heating. High-pressure x-ray diffraction data show that CaO3 crystal forms at 35 GPa and persists down to 20 GPa on decompression. Analysis of charge states reveals a formal oxidation state of -2 for ozone anions in CaO3. These findings unravel the ozonide chemistry at high pressure and offer insights for elucidating prominent seismic anomalies and oxygen cycles in Earth's interior. We further predict multiple reactions producing CaO3 by geologically abundant mineral precursors at various depths in Earth's mantle
Preparation and evaluation of lactic acid acylated exenatide and its long-acting preparation
Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
AbstractMitoxantrone (MX) can induce the immunogenic-cell death (ICD) of tumor cells and activate anti-tumor immune responses. However, it can also cause high expression of indole amine 2, 3-dioxygenase (IDO) during ICD, leading to T-cell apoptosis and a weakened immune response. An IDO inhibitor, 1-methyl tryptophan (1-MT), can inhibit the activity of IDO caused by MX, resulting in enhanced chemo-immunotherapy. Here, MX-1-MT was connected by ester bond which could be broken in an acidic tumor microenvironment. MX-1-MT was combined with polyethylene glycol (PEG) via a disulfide bond which could be reduced by glutathione overexpressed in tumors, thereby accelerating drug release at target sites. Folic acid-modified distearoyl phosphoethanolamine-polyethylene glycol (DSPE-PEG-FA) was introduced to form targeting micelles. The micelles were of uniform particle size, high stability, and high responsiveness. They could be taken-up by drug-resistant MCF-7/ADR cells, displayed high targeting ability, and induced enhanced cytotoxicity and ICD. Due to 1-MT addition, micelles could inhibit IDO. In vivo studies demonstrated that micelles could accumulate in the tumor tissues of nude mice, resulting in an enhanced antitumor effect and few side-effects
Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity
AbstractDoxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX
Multivesicular liposomes for sustained release of bevacizumab in treating laser-induced choroidal neovascularization
Bevacizumab is an anti-vascular endothelial growth factor drug that can be used to treat choroidal neovascularization (CNV). Bevacizumab-loaded multivesicular liposomes (Bev-MVLs) have been designed and developed to increase the intravitreal retention time of bevacizumab and reduce the number of injection times. In this study, Bev-MVLs with high encapsulation efficiency were prepared by double emulsification technique, and antibody activity was determined. The results revealed that 10% of human serum albumin (HSA) could preserve the activity of bevacizumab. In vitro release of Bev-MVLs appeared to be in a more sustained manner, the underlying mechanisms of Bev-MVLs indicated that bevacizumab was released from MVLs through diffusion and erosion. Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that bevacizumab could retain its structural integrity after being released from MVLs in vitro. In vivo imaging was used to evaluate the retention time of antibody in rat eyes, while pharmacokinetic analysis was performed on rabbit eyes. These results indicated that Bev-MVLs exhibited sustained release effects as compared to bevacizumab solution (Bev-S). Bev-MVLs could effectively inhibit the thickness of CNV lesion as compared to Bev-S at 28 days after treatment. Furthermore, these data suggest that Bev-MVLs are biologically feasible to increase the retention time of bevacizumab in vitreous humor. This novel Bev-MVLs may therefore serve as a promising sustained release drug delivery system for the treatment of CNV
Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting
Glioblastoma is the most common malignant brain tumor. Efficient delivery of drugs targeting glioblastomas remains a challenge. Ephrin type-A receptor 3 (EPHA3) tyrosine kinase antibody-modified polylactide-co-glycolide (PLGA) nanoparticles (NPs) were developed to target glioblastoma via nose-to-brain delivery. Anti-EPHA3-modified, TBE-loaded NPs were prepared using an emulsion-solvent evaporation method, showed a sustained in vitro release profile up to 48 h and a mean particle size of 145.9 ± 8.7 nm. The cellular uptake of anti-EPHA3-modified NPs by C6 cells was significantly enhanced compared to that of nontargeting NPs (p < .01). In vivo imaging and distribution studies on the glioma-bearing rats showed that anti-EPHA3-modified NPs exhibited high fluorescence intensity in the brain and effectively accumulated to glioma tissues, indicating the targeting effect of anti-EPHA3. Glioma-bearing rats treated with anti-EPHA3-modified NPs resulted in significantly higher tumor cell apoptosis (p < .01) than that observed with other formulations and prolonged the median survival time of glioma-bearing rats to 26 days, which was 1.37-fold longer than that of PLGA NPs. The above results indicated that anti-EPHA3-modified NPs may potentially serve as a nose-to-brain drug carrier for the treatment of glioblastoma
Multivesicular liposomes for sustained release of bevacizumab in treating laser-induced choroidal neovascularization
Pressure-Induced Phase Transformation, Reversible Amorphization, and Anomalous Visible Light Response in Organolead Bromide Perovskite
Hydrostatic pressure, as an alternative
of chemical pressure to
tune the crystal structure and physical properties, is a significant
technique for novel function material design and fundamental research.
In this article, we report the phase stability and visible light response
of the organolead bromide perovskite, CH<sub>3</sub>NH<sub>3</sub>PbBr<sub>3</sub> (MAPbBr<sub>3</sub>), under hydrostatic pressure
up to 34 GPa at room temperature. Two phase transformations below
2 GPa (from <i>Pm</i>3Ì…<i>m</i> to <i>Im</i>3Ì…, then to <i>Pnma</i>) and a reversible
amorphization starting from about 2 GPa were observed, which could
be attributed to the tilting of PbBr<sub>6</sub> octahedra and destroying
of long-range ordering of MA cations, respectively. The visible light
response of MAPbBr<sub>3</sub> to pressure was studied by in situ
photoluminescence, electric resistance, photocurrent measurements
and first-principle simulations. The anomalous band gap evolution
during compression with red-shift followed by blue-shift is explained
by the competition between compression effect and pressure-induced
amorphization. Along with the amorphization process accomplished around
25 GPa, the resistance increased by 5 orders of magnitude while the
system still maintains its semiconductor characteristics and considerable
response to the visible light irradiation. Our results not only show
that hydrostatic pressure may provide an applicable tool for the organohalide
perovskites based photovoltaic device functioning as switcher or controller,
but also shed light on the exploration of more amorphous organometal
composites as potential light absorber