Graft copolymers have unique application scenarios in the field of high-performance thermoplastic elastomers, resins and rubbers. β-myrcene (My) is a biomass monomer derived from renewable plant ...resources, and its homopolymer has a low glass transition temperature and high elasticity. In this work, a series of tapered copolymers P(My-
-AMS)
(k = 1, 2, 3) were first synthesized in cyclohexane by one-pot anionic polymerization of My and α-methyl styrene (AMS) using sec-BuLi as the initiator. PAMS chain would fracture when heated at high temperature and could endow the copolymer with thermal degradation property. The effect of the incorporation of AMS unit on the thermal stability and glass transition temperature of polymyrcene main chain was studied. Subsequently, the double bonds in the linear copolymers were partially epoxidized and hydroxylated into hydroxyl groups to obtain hydroxylated copolymer, which was finally used to initiate the ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) to synthesize the graft copolymer with PCL as the side chain. All these copolymers before and after modifications were characterized by proton nuclear magnetic resonance (
H NMR), gel permeation chromatography (GPC), thermogravimetry analysis (TGA), and differential scanning calorimeter (DSC).
Frank–Kasper (F-K) and quasicrystal phases were originally identified in metal alloys and only sporadically reported in soft materials. These unconventional sphere-packing schemes open up ...possibilities to design materials with different properties. The challenge in soft materials is how to correlate complex phases built from spheres with the tunable parameters of chemical composition and molecular architecture. Here, we report a complete sequence of various highly ordered mesophases by the self-assembly of specifically designed and synthesized giant surfactants, which are conjugates of hydrophilic polyhedral oligomeric silsesquioxane cages tethered with hydrophobic polystyrene tails. We show that the occurrence of these mesophases results from nanophase separation between the heads and tails and thus is critically dependent on molecular geometry. Variations in molecular geometry achieved by changing the number of tails from one to four not only shift compositional phase boundaries but also stabilize F-K and quasicrystal phases in regions where simple phases of spheroidal micelles are typically observed. These complex self-assembled nanostructures have been identified by combining X-ray scattering techniques and real-space electron microscopy images. Brownian dynamics simulations based on a simplified molecular model confirm the architecture-induced sequence of phases. Our results demonstrate the critical role of molecular architecture in dictating the formation of supramolecular crystals with “soft” spheroidal motifs and provide guidelines to the design of unconventional self-assembled nanostructures.
The acid-cleavable amphiphilic prodrug DOX-PEG-DOX self-assemble to form nanoparticles and enter the cell by endocytosis for the pH-triggered intracellular delivery of DOX.
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PEGylated ...prodrug, covalent attaching polyethylene glycol (PEG) polymer chains to therapeutic drugs, is one of the most promising techniques to improve the water-solubility, stability, and therapeutic effect of drugs. In this study, three PEGylated acid-sensitive prodrugs DOX-PEG-DOX with different molecular weights, were prepared via Schiff-base reaction between aldehyde-modified PEG and the amino groups of doxorubicin (DOX). This kind of amphiphilic polymeric prodrug could be self-assemble into nanoparticles in aqueous solution. The average particle size and morphologies of the prodrug nanoparticles under different pH conditions were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. It turned out that the nanoparticles could be kept stable in the physiological environment, but degraded in acidic medium. Subsequently, we also investigated in vitro drug release behavior and found that the prodrug had acid-sensitive property. The cytotoxicity and intracellular uptake assays revealed that the prodrugs could rapidly internalized by HeLa or HepG2 cells to release DOX and effectively inhibited the proliferation of the tumor cells, which have the potential for use in cancer therapy.
Polymeric micelles have demonstrated wide utility for chemodrug delivery, which however, still suffer from shortcomings such as undesired drug loading, disassembly upon dilution, pre-leakage of drug ...cargoes during systemic circulation, and lack of cancer-selective drug release. Herein, a poly(ethylene glycol) (PEG)-polyphosphoester-based, reactive oxygen species (ROS)-responsive, core-cross-linked (CCL) micellar system was developed to encapsulate both chemodrug (doxorubicin, Dox) and photosensitizer (chlorin e6, Ce6). The hydrophobic core of the micelles was cross-linked via a thioketal (TK)-containing linker, which notably enhanced the drug loading and micelle stability. In tumor cells, far-red light irradiation of Ce6 generated ROS to cleave the TK linkers and disrupt the micelle cores. As such, micelles were destabilized and Dox release was promoted, which thereafter imparted synergistic anti-cancer effect with ROS-mediated photodynamic therapy. This study provides an effective approach to realize the precise control over drug loading, formulation stability, and cancer-selective drug release using polymeric micelles, and would render promising utilities for the programmed anti-cancer combination therapy.
The up-regulated FOXD3-AS1 sponged miR-765 to elevate the expression of BCL2L13, resulting in cell apoptosis through increasing the expression of BAX, c-PARP and c-caspase-3 and decreasing the ...expression of Bcl-2 after cerebral ischemia, leading to ischemia brain injury. Whereas, FOXD3-AS1 inhibition or miR-765 overexpression could alleviate cell apoptosis and protect against ischemia brain injury via regulation of FOXD3-AS1/miR-765/BCL2L13 axis.
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•Down-regulated FOXD3-AS1 played a neuronal protection role.•FOXD3-AS1 acted as a ceRNA for miR-765, elevating BCL2L13 expression.•FOXD3-AS1 inhibition or miR-765 overexpression could alleviate cell apoptosis•FOXD3-AS1 inhibition or miR-765 overexpression could protect against ischemia brain injury.
Long non-coding RNAs (lncRNAs) FOXD3-AS1 was reported to be increased in cardiomyocyte ischemic injury. However, its role and underlying molecular mechanism in ischemic stroke remain unknown. This study was to investigate the role of FOXD3-AS1 in cerebral ischemia/reperfusion injury.
The expression of FOXD3-AS1 and miR-765 were measured with qRT-PCR. The shared putative miR-765 binding sites both in BCL2L13 and FOXD3-AS1 were identified with bioinformatics, luciferase reporter assay and RNA immunoprecipitation. Apoptosis and its related proteins were detected by TUNEL assay, Hoechst 33,258 staining, flow cytometry and western blot. Infarct volume and the neurological status were evaluated with TTC staining and neurologic deficit score, respectively.
The up-regulation of FOXD3-AS1 and down-regulation of miR-765 were found in both mouse brains after cerebral ischemia/reperfusion (I/R) and neuroblastoma cells of neuro-2A (N2a) after oxygen-glucose deprivation/reoxygenation (OGD/R). Moreover, the overexpression of miR-765 reduced N2a cell apoptosis caused by OGD/R. MiR-765 could target BCL2L13 directly. In addition, we found that FOXD3-AS1 bound to miR-765 directly, acting as a ceRNA to modulate the expression of BCL2L13. Overexpression of FOXD3-AS1 antagonized the inhibitory impact of miR-765 on the expression of BCL2L13 and the apoptosis of N2a cells treated with OGD/R, while FOXD3-AS1 knockdown promoted the inhibitory impact of miR-765 on the expression of BCL2L13 and the apoptosis of N2a cells treated with OGD/R. Furthermore, we found that neurological deficits and brain injury induced by I/R in vivo were attenuated by FOXD3-AS1 knockdown.
We verified a critical signaling pathway of FOXD3-AS1/miR-765/BCL2L13 in regulating cerebral ischemia/reperfusion injury.
Radiation is one of the most widely used methods for cancer diagnosis and therapy. Herein, we report a new type of radiation sensitizer (Fc-PEG) by a facile one-step reaction of conjugating the ...hydrophilic PEG chain with hydrophobic ferrocene molecule. The chemical composition and structure of Fc-PEG have been thoroughly characterized by FT-IR, NMR, GPC, and MALDI-TOF mass spectrometry. This Fc-PEG conjugate could self-assemble in aqueous solution into spherical aggregates, and it was found that the exposure to 4 Gy of X-ray radiation have little influence on the shape and size of these aggregates. After the chemical bonding with PEG chains, the uptake level of Fe element could be enhanced via the formation of aggregates. The live/dead, CCK-8, as well as apoptosis assays, indicated that the death of cancer cells can be obviously increased by X-ray radiation after the incubation of these Fc-based nanoconjugates, which might be served as the radiation sensitizer toward cancer cells. We suggest that this radiosensitizing effect comes from the enhancement of reactive oxygen specimen (ROS) level as denoted by both flow cytometric and fluorescence microscopic analysis. The enhanced radiation sensitivity of cancer cells is contributed by the synergic effect of Fe-induced radiation-sensitizing and the increased uptake of nanoconjugates after polymeric grafting.
Excessive differentiation of osteoclasts contributes to the disruption of bone homeostasis in inflammatory bone diseases. Methyltransferase-like 3 (METTL3), the core methyltransferase that installs ...an N6-methyladenosine (m
A) modification on RNA, has been reported to participate in bone pathophysiology. However, whether METTL3-mediated m
A affects osteoclast differentiation in inflammatory conditions remains unelucidated. In this study, we observed that the total m
A content and METTL3 expression decreased during LPS-induced osteoclastogenesis. After knocking down METTL3, we found reduced levels of the number of osteoclasts, osteoclast-related gene expression and bone resorption area. A METTL3 deficiency increased osteoclast apoptosis and pro-apoptotic protein expression. RNA sequencing analysis showed that differentially expressed genes in METTL3-deficient cells were mainly associated with the mitochondrial function. The expression of the mitochondrial function-related genes, ATP production and mitochondrial membrane potential decreased after METTL3 knockdown. Moreover, the most obviously upregulated gene in RNA-Seq was
, which encoded the iNOS protein to induce nitric oxide (NO) synthesis. METTL3 knockdown increased the levels of
mRNA, iNOS protein and NO content. NOS inhibitor L-NAME rescued the inhibited mitochondrial function and osteoclast formation while suppressing osteoclast apoptosis in METTL3-silenced cells. Mechanistically, a METTL3 deficiency promoted the stability and expression of
mRNA, and similar results were observed after m
A-binding protein YTHDF1 knockdown. Further in vivo evidence revealed that METTL3 knockdown attenuated the inflammatory osteolysis of the murine calvaria and suppressed osteoclast formation. In conclusion, these data suggested that METTL3 knockdown exacerbated iNOS/NO-mediated mitochondrial dysfunction by promoting a
mRNA stability in a YTHDF1-dependent manner and further inhibited osteoclast differentiation and increased osteoclast apoptosis in inflammatory conditions.
Novel pH- and temperature-responsive double-hydrophilic diblock copolymers, poly(ethylethylene phosphate)-block-poly2-(dimethylamino)ethyl methacrylate (PEEP-b-PDMAEMA), have been synthesized via the ...combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The PEEP block with a bromine-terminated end (PEEP-Br) was first prepared by ROP of 2-ethoxy-2-oxo-1,3,2-dioxaphospholane (EEP) using 2-hydroxyethyl 2-bromoisobutyrate as a bifunctional initiator and stannous octoate as a catalyst. ATRP was then used to polymerize DMAEMA monomer in a methanol/water mixture with PEEP-Br as a macroinitiator, resulting in diblock copolymers of PEEP-b-PDMAEMA. Their chemical structures were respectively characterized by 1H NMR, 13C NMR, 31P NMR, and FT-IR. Their molar mass distributions were determined by gel permeation chromatography (GPC). The critical aggregation concentration (cac) of PEEP-b-PDMAEMA in aqueous solution, which was measured by the fluorescence probe technique, depends on the block composition. The results measured by static laser light scattering (LLS), dynamic light scattering (DLS), and transmission electron microscopy (TEM) reveal that these diblock copolymers are able to self-assemble into aggregates with different particle sizes and morphologies in aqueous solutions, depending on various pH media. On the other hand, the UV−vis measurement shows that these diblock copolymers exhibit a reproducible temperature-responsive behavior with a lower critical solution temperature (LCST) that is tunable by the block composition and pH. In addition, agarose gel retardation assays, TEM, and zeta potential measurements demonstrate that such double-hydrophilic diblock copolymers can effectively condense DNA, potentially useful for the gene delivery.
In this paper, SiO2 nanoparticles were first modified with (heptadecafluoro-1, 1, 2, 2-tetradecyl)trimethoxysilane (TSL-8233) to improve its dispersibility and compatibility in the polymer matrix. ...The structure and property of SiO2 nanoparticles before and after modification were characterized by FT-IR, TGA and TEM analysis. Together with poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP) and polypropylene (PP) nonwoven fabric, these SiO2 nanoparticles were then used to construct two kinds of composite separators (abbreviated as PHS for pristine SiO2 and PHS-8233 for modified TSL-8233@SiO2). The morphology, electrolyte uptake, ionic conductivity and electrochemical properties of the composite separators were analyzed by SEM analysis, AC impedance measurements, charge–discharge cycle and C-rate tests, respectively. These results indicated that PHS-8233 composite separator exhibited an improved pore distribution, electrolyte uptake (280wt%) and ionic conductivity (1.90mScm−1). Even more importantly, LiFePO4/Li cells assembled with PHS-8233 composite separator displayed remarkable C-rate performance, which showed an enhancement in the chemical stability and discharge capacity. The capacity kept above 144mAhg−1 after 100 charge–discharge cycles.
•Fluorinated SiO2 nanoparticles showed better dispersibility and compatibility.•The composite separator exhibited improved physical and electrochemical properties.•The discharge capacity of cells kept about 144mAhg−1 after 100 cycles.
A series of parent block copolyesters poly(ɛ-caprolactone)-block-poly2-(2-oxo-1, 3, 2-dioxaphospholoyloxy)ethyl acrylate (PCL-b-POPEA) with different block lengths have been synthesized by ...ring-opening polymerization (ROP) and four kinds of mercaptans were then used in the postpolymerization modification via Michael-type addition reaction, resulting in several block copolyesters with various functionalities (e.g., hydroxyl, carboxyl, amine, and amino acid) in their pendant groups. The chemical structures of these block copolymers were characterized by FT-IR, NMR spectroscopy and GPC analysis. The self-assembly behaviors of PCL-b-POPEA have been studied by fluorescence probe technique, transmission electron microscopy (TEM) and high-performance particle size (HPPS) instrument. In vitro cytotoxicity test indicated that the block copolymers possess good biocompatibility. Initial in vitro drug loading and release studies using Doxorubicin (DOX) as a model drug demonstrated a faster release in the presence of phosphodiesterase I as compared to the system without enzyme. Moreover, it was found that DOX-loaded nanoparticles displayed higher inhibition to KB cell proliferation in comparison with free DOX. Therefore, the combination of ROP and Michael-type addition reaction provides a general access to various types of multifunctional and biodegradable materials.
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