Preparation of poly(ethylene glycol)/polylactide hybrid fibrous scaffolds for bone tissue engineering

Polylactide (PLA) electrospun fibers have been reported as a scaffold for bone tissue engineering application, however, the great hydrophobicity limits its broad application. In this study, the hybrid amphiphilic poly(ethylene glycol) (PEG)/hydrophobic PLA fibrous scaffolds exhibited improved morphology with regular and continuous fibers compared to corresponding blank PLA fiber mats. The prepared PEG/PLA fibrous scaffolds favored mesenchymal stem cell (MSC) attachment and proliferation by providing an interconnected porous extracellular environment. Meanwhile, MSCs can penetrate into the fibrous scaffold through the interstitial pores and integrate well with the surrounding fibers, which is very important for favorable application in tissue engineering. More importantly, the electrospun hybrid PEG/PLA fibrous scaffolds can enhance MSCs to differentiate into bone-associated cells by comprehensively evaluating the representative markers of the osteogenic procedure with messenger ribonucleic acid quantitation and protein analysis. MSCs on the PEG/PLA fibrous scaffolds presented better differentiation potential with higher messenger ribonucleic acid expression of the earliest osteogenic marker Cbfa-1 and mid-stage osteogenic marker Col I. The significantly higher alkaline phosphatase activity of the PEG/PLA fibrous scaffolds indicated that these can enhance the differentiation of MSCs into osteoblast-like cells. Furthermore, the higher messenger ribonucleic acid level of the late osteogenic differentiation markers OCN (osteocalcin) and OPN (osteopontin), accompanied by the positive Alizarin red S staining, showed better maturation of osteogenic induction on the PEG/PLA fibrous scaffolds at the mineralization stage of differentiation. After transplantation into the thigh muscle pouches of rats, and evaluating the inflammatory cells surrounding the scaffolds and the physiological characteristics of the surrounding tissues, the PEG/PLA scaffolds presented good biocompatibility. Based on the good cellular response and excellent osteogenic potential in vitro, as well as the biocompatibility with the surrounding tissues in vivo, the electrospun PEG/PLA fibrous scaffolds could be one of the most promising candidates in bone tissue engineering

A novel Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) grafted Polyethyleneimine(PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study

<p>Abstract</p> <p>Background</p> <p>Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection <it>in vitro</it>. However, its <it>in vivo </it>application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting.</p> <p>Results</p> <p>Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) (PCFC) was synthesized by ring-opening polymerization, and PCFC-<it>g</it>-PEI was obtained by Michael addition reaction with GMA-PCFC-GMA and polyethyleneimine (PEI, 25 kD). The prepared PCFC-<it>g</it>-PEI was characterized by ¹H-NMR, SEC-MALLS. Meanwhile, DNA condensation, DNase I protection, the particle size and zeta potential of PCFC-<it>g</it>-PEI/DNA complexes were also determined. According to the results of flow cytometry and MTT assay, the synthesized PCFC-<it>g</it>-PEI, with considerable transfection efficiency, had obviously lower cytotoxicity against 293 T and A549 cell lines compared with that of PEI 25 kD.</p> <p>Conclusion</p> <p>The cytotoxicity and <it>in vitro </it>transfection study indicated that PCFC-<it>g</it>-PEI copolymer prepared in this paper was a novel gene delivery system with lower cytotoxicity and considerable transfection efficiency compared with commercial PEI (25 kD).</p

Amphiphilic Polymer-Modified Uniform CuFeSe2 Nanoparticles for CT/MR Dual-Modal Imaging

Recently, magnetic photothermal nanomaterials have attracted much attention in the diagnosis and treatment of cancer. In this study, we developed the ultrasmall magnetic CuFeSe2 nanoparticles for CT/MR dual-modal imaging. By controlling the reaction time and condition, CuFeSe2 nanoparticles were synthesized by a simple directly aqueous method. After modification with copolymer methoxy polyethylene glycol-polycaprolactone (MPEG-PCL), the obtained MPEG-PCL@CuFeSe2 nanoparticles showed excellent water solubility, colloidal stability, and biocompatibility. In addition, they also exhibited superparamagnetism and X-ray’s characteristics. For these properties, they will become ideal nanomaterials for CT/MR dual-modal imaging

Effect of low-dose total-body radiotherapy on immune microenvironment

The history of low-dose total-body irradiation (LTBI) as a means of radiotherapy for treating malignant tumors can be traced back to the 1920s. Despite this very low total dose, LTBI can induce long-term remissions. Tumor cells are known to change and maintain their own survival and development conditions through autocrine and paracrine signaling. LTBI can change the tumor microenvironment, enhance the infiltration of activated T cells, and trigger inflammatory processes. LTBI-mediated immune response can exert systemic long-term anti-tumor effects, and can induce tumor regression at the primary site and metastatic sites. With a continuous improvement in the anti-tumor immune microenvironment in the field of tumor therapy, LTBI provides more choices to comprehensively treat of tumors. The present study aimed to explore the experimental research mechanism of LTBI and immune microenvironment, and discuss the difficulties and development prospects of applying LTBI to tumor treatment

Thermal Stability of Self-Assembled 3-Aminopropyltrimethoxysilane Diffusion Barrier Terminated by Carboxyl Groups

The carboxyl-terminated 3-aminopropyltrimethoxysilane (APTMS) self-assembled monolayer (SAM) diffusion barrier was prepared onto a Si substrate via molecular self-assembly and graft modification technology. The SAM was afterward coated with a copper film via radio-frequency (RF) magnetron sputtering. In order to study the thermal stability of the diffusion barrier, the sample was subsequently annealed for 60 min in an Ar environment at the temperatures of 350 °C, 400 °C, 450 °C, 500 °C, and 550 °C. The results revealed that carboxyl modification enabled one to increase the barrier breakdown temperature of the APTMS diffusion barrier layer by about 100 °C, which was sufficient to effectively inhibit the copper diffusion at 500 °C

Zinc finger and SCAN domain-containing protein 18 is a potential DNA methylation-modified tumor suppressor and biomarker in breast cancer

IntroductionZinc finger and SCAN domain-containing protein 18 (ZSCAN18) has been investigated as a putative biomarker of multiple human cancers. However, the expression profile, epigenetic modification, prognostic value, transcription regulation, and molecular mechanism of ZSCAN18 in breast cancer (BC) remain unknown.MethodsIn the study, we present an integrated analysis of ZSCAN18 in BC based on public omics datasets with the use of multiple bioinformatics tools. Genes potentially regulated through restoration of ZSCAN18 expression in MDA-MB-231 cells were investigated to identify pathways associated with BC.ResultsWe observed that ZSCAN18 was downregulated in BC and mRNA expression was significantly correlated with clinicopathological parameters. Low expression of ZSCAN18 was found in the HER2-positive and TNBC subtypes. High expression of ZSCAN18 was associated with good prognosis. As compared to normal tissues, the extent of ZSCAN18 DNA methylation was greater with fewer genetic alterations in BC tissues. ZSCAN18 was identified as a transcription factor that might be involved in intracellular molecular and metabolic processes. Low ZSCAN18 expression was associated with the cell cycle and glycolysis signaling pathway. Overexpression of ZSCAN18 inhibited mRNA expression of genes associated with the Wnt/β-catenin and glycolysis signaling pathways, including CTNNB1, BCL9, TSC1, and PFKP. ZSCAN18 expression was negatively correlated with infiltrating B cells and dendritic cells (DCs), as determined by the TIMER web server and reference to the TISIDB. ZSCAN18 DNA methylation was positively correlated with activated B cells, activated CD8+ and CD4+ T cells, macrophages, neutrophils, and activated DCs. Moreover, five ZSCAN18-related hub genes (KDM6B, KAT6A, KMT2D, KDM1A, and HSPBP1) were identified. ZSCAN18, ZNF396, and PGBD1 were identified as components of a physical complex.ConclusionZSCAN18 is a potential tumor suppressor in BC, as expression is modified by DNA methylation and associated with patient survival. In addition, ZSCAN18 plays important roles in transcription regulation, the glycolysis signaling pathway, and the tumor immune microenvironment

Intratumoral injection of anlotinib hydrogel enhances antitumor effects and reduces toxicity in mouse model of lung cancer

This study was conducted to determine the antitumor effects and ability of an anlotinib (AL) hydrogel (AL–HA–Tyr) to reduce toxicity in a mouse model of Lewis lung cancer (LLC). We constructed a drug carrier system for AL, verified its effectiveness and systemic safety, and provided a preliminary experimental foundation for clinical carrier transformation. AL–HA–Tyr was prepared by encapsulating AL with hyaluronic acid–tyramine (HA–Tyr) conjugates. Colony and tube formation assays showed that AL–HA–Tyr restrained the proliferation of human umbilical vein endothelial cells (HUVECs) and LLC cells, respectively, in vitro, and that AL exerted significant anti-angiogenesis and anti-tumor effects. The invasion and migration of HUVECs and LLC cells were efficiently suppressed by AL according to transwell assays. HUVEC and LLC cell-cycle and apoptosis analysis clarified the direct anti-tumor effects of AL–HA–Tyr. Mice engrafted with LLC cells in vivo were administered oral saline, oral AL, or an intratumoral injection of HA–Tyr or AL–HA–Tyr. The results showed that AL–HA–Tyr obviously reduced visceral toxicity and decreased Ki67 and VEGF-A expression in tumor cells compared with AL. Furthermore, AL–HA–Tyr significantly prolonged the survival of tumor-bearing mice. Overall, AL–HA–Tyr enhanced antitumor effects and reduced toxicity in the LLC model. It provided a foundation for the clinical transformation of drug carrier systems

Honokiol-loaded polymeric nanoparticles: an active targeting drug delivery system for the treatment of nasopharyngeal carcinoma

The purpose of this study was to develop a novel drug delivery system for a sustained and targeted delivery of honokiol (HK) to the nasopharyngeal carcinoma (NPC) HNE-1 cell lines, since the folate receptor (FR) is over-expressed on their surface. Emulsion solvent evaporation was used to develop the active targeting nanoparticles-loaded HK (ATNH) using copolymerpoly (ɛ-caprolactone)-poly (ethyleneglycol)-poly (ɛ-caprolactone) (PCEC), which was modified with folate (FA) by introducing Polythylenimine (PEI). ATNH characterization, including particle size distribution, morphology, drug loading, encapsulation efficiency and drug release, was performed. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) were employed to evaluate the shape and construction, respectively. MTT assay, cell uptake study and apoptosis test were assayed to detect the antitumor properties and targeting uptake by HNE-1 cells in vitro. Cell-cycle redistribution, 18 F-FDG PET/CT and immunohistochemistry were performed in vivo. The ATNH we developed were successfully synthesized and showed a suitable size distribution, high encapsulation efficiency, gradual release, and targeting uptake by the cells in vitro. Moreover, ATNH significantly inhibited tumor growth, metabolism, proliferation, micro-vessel generation, and caused cell-cycle arrest at G1 phase. Thus, these nanoparticles we developed might represent a novel formulation for HK delivery and a promising potential therapy in the treatment of cancer

Self-assembled dihydroartemisinin nanoparticles as a platform for cervical cancer chemotherapy

Dihydroartemisinin (DHA) is a potent anti-cancer drug that has limited clinical applications due to poor water solubility and low bioavailability. We designed a biodegradable poly(ethylene glycol) methyl ether-poly(ε-caprolactone) (MPEG-PCL) micelle carrier for DHA using the self-assembly method. The DHA/MPEG-PCL nanoparticles were spherical with an average particle size of 30.28 ± 0.27 nm, and released the drug in a sustained manner in aqueous solution. The drug-loaded nanoparticles showed dose-dependent toxicity in HeLa cells by inducing cycle arrest and apoptosis. Furthermore, compared to free DHA, the DHA/MPEG-PCL nanoparticles showed higher therapeutic efficacy and lower toxicity in vivo, and significantly inhibited tumor growth and prolonged the survival of tumor-bearing nude mice. In addition, the tumor tissues of the DHA/MPEG-PCL-treated mice showed a marked decline in the in situ expression of proliferation and angiogenesis markers. Taken together, the self-assembled DHA/MPEG-PCL nanoparticles are a highly promising delivery system for targeted cancer treatment