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ACS Applied Nano Materials · 2020 · IF 0

Lipophilic Red-Emitting Oligomeric Organic Dots for Moisture Detection and Cell Imaging

Gancheng Zuo,Yingzhi Jiao,Ruru Gao,Aming Xie,Xihao Pan,Ting Su,Wei Dong

The development of self-assembled organic dots (ODs) with lipophilic fluorescent properties has significant potential in various applications, especially in sensing and bioimaging. Herein, we report a one-pot gram-scale synthesis of lipophilic red-emitting oligomeric L-ODs with high quantum yield (39.3%), which is prepared by a solvothermal condensation of o-phenylenediamine and L-tartaric acid. Interestingly, as-prepared ODs show no solid and aqueous emission but intense red fluorescence in the majority of organic solvents. The titration of water indicates that ODs can be applied to the moisture detection of organic solvent. And since ODs exhibit excellent biocompatibility, they are successfully used as a lipophilic red-emitting imaging reagent. Furthermore, contrast experiment and theoretical simulation are adopted to reveal the photoluminescence mechanism of L-ODs. Thus, the hydrogen-bond-induced red-shift of the benzimidazole intermediate is thought to be the main reason for the intense red-emitting fluorescence of the prepared L-ODs. The gram-scale and simple reaction without any purification suggests that these lipophilic oligomeric ODs have a promising prospect in the application of fluorescent probe and lipophilic environment imaging.

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CARBON · 2021 · IF 9.594

Red emissive two-photon carbon dots: Photodynamic therapy in combination with real-time dynamic monitoring for the nucleolus

Shangzhao Yi,Simin Deng,Xiaolu Guo,Congcong Pang,Jinyan Zeng,Shichen Ji,Hong Liang,Xing-Can Shen,Bang-Ping Jiang

Treatment in combination with real-time monitoring of dynamic organelle changes is of great significance for evaluating therapeutic efficacy. However, it remains highly challenging to realize such specific treatment and monitoring in organelles. Herein, we developed one kind of red emissive two-photon carbon dots (TP-CDs) via an N doping strategy for nucleolus-targeted treatment combined with real-time monitoring of dynamic changes in the nucleolus. In the TP-CD system, N doping endows TP-CDs with intrinsic two-photon excitation, red emission at 605 nm, and singlet oxygen ( 1 O 2 ) production under 638 nm laser irradiation. More importantly, N heterocycles induced by doping offers significant affinity for TP-CDs toward RNA to realize specific self-targeting toward nucleolus and fluorescence variation during the photodynamic therapy (PDT) via the cleaving of RNA chain by 1 O 2 to dissociate [email protected] complex. By combining 1 O 2 production, fluorescent variation during the PDT process, long-wavelength excitation and emission characteristics, as well as specific self-targetability of nucleolus, TP-CDs can be considered as a kind of “smart” CDs to realize treatment in combination of real-time dynamic changes in nucleolus for the first time.

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ACS Applied Materials & Interfaces · 2017 · IF 7.504

Nano Ag/ZnO-Incorporated Hydroxyapatite Composite Coatings: Highly Effective Infection Prevention and Excellent Osteointegration

Yanzhe Zhang,Xiangmei Liu,Zhaoyang Li,Shengli Zhu,Xubo Yuan,Zhenduo Cui,Xianjin Yang,Paul K. Chu,Shuilin Wu

Interfacial characteristics play an important role in infection prevention and osteointegration of artificial bone implants. In this work, both Ag nanoparticles (AgNPs) and ZnO NPs are incorporated into hydroxyapatite (HA) nanopowders and deposited onto Ti6Al4V (Ti6) implants by laser cladding. The composite coatings possess a hierarchical surface structure with homogeneous distributions of Ag and ZnO. The Ag and ZnO NPs that are immobilized by laser cladding ensure long-term and gradual release of Ag and Zn ions at low cumulative concentrations of 36.2 and 56.4 μg/L after immersion for 21 days. A large concentration of Ag released initially increases the cytotoxicity but the large initial ZnO content enhances the cell viability and osteogenetic ability. The nano Ag/ZnO-embedded HA coating (Ag/ZnO/HA = 7:3:90 wt %, namely Ag7ZnO3HA) exhibits optimal antibacterial efficacy and osteogenetic capability, as exemplified by the broad spectrum antibacterial efficacy of 96.5 and 85.8% against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively, together with enhanced osteoinductivity with higher alkaline phosphatase (ALP) activity of 134.60 U/g protein compared to 70.79 U/g protein for the untreated implants after culturing for 7 days. The rabbit femoral implant model further confirms that the optimized composite coating accelerates the formation of new bone tissues indicating 87.15% of the newly formed bone area and osteointegration showing 83.75% of the bone–implant contact area even in the presence of injected S. aureus. The laser-cladded Ag7ZnO3HA composite coatings are promising metallic implants with excellent intrinsic antibacterial activity and osteointegration ability.

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Polymer Chemistry · 2014 ·Vol. 5 ·期 20 ·5906-5919 · IF 5.368

Surface-engineered nanogel assemblies with integrated blood compatibility, cell proliferation and antibacterial property: towards multifunctional biomedical membranes

Yi Xia,Chong Cheng,Rui Wang,Hui Qin,Yi Zhang,Lang Ma,Hong Tan,Zhongwei Gu,Changsheng Zhao

In this study, novel 3D multifunctional nanolayers are fabricated on biomedical membrane surfaces via layer-by-layer (LBL) self-assembly of nanogels and heparin-like polymers. To integrate long-term antibacterial activity, Ag nanoparticles embedded in nanogels were first prepared. Then, the Ag nanogels were assembled onto membrane surfaces by electrostatic interaction. To obtain a heparin-mimicking surface, the as-prepared nanogel-coated membranes were further assembled with heparin-like polymers by two different processes. The results indicated that the obtained nanogel and heparin-mimicking polymer assembled membranes exhibited 3D surface morphologies. Systematical blood compatibility and antithrombotic evaluations revealed that the functionalized membranes showed increased hydrophilicity, decreased protein adsorption, and prolonged clotting times and greatly suppressed platelet adhesion compared to pristine membrane. The cell culture observations demonstrated that the pristine, nanogel-assembled, and heparin-mimicking membranes showed different performances in terms of endothelial cell proliferation and adhesion morphology. The results of the antibacterial study indicated that the functionalized membranes exhibited significant inhibition capability for Escherichia coli and Staphylococcus aureus. In general, the surface coassembly of nanogels and heparin-mimicking polymers produced functionalized membranes with integrated blood compatibility, cell proliferation and antibacterial properties for multiple applications, which may advance the fabrication of biomedical devices by surface assembly of functional nanogels.

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Acta Biomaterialia · 2022 · IF 10.633

Bioinspired zwitterionic microgel-based coating: Controllable microstructure, high stability, and anticoagulant properties

Mengmeng Yao,Xia Sun,Zhicheng Guo,Zhongming Zhao,Zhuojun Yan,Fanglian Yao,Hong Zhang,Junjie Li

Zwitterionic polymers have shown promising results in non-fouling and preventing thrombosis. However, the lack of controlled surface coverage hinders their application for biomedical devices. Inspired by the natural biological surfaces, a facile zwitterionic microgel-based coating strategy is developed by the co-deposition of poly (sulfobetaine methacrylate-co-2-aminoethyl methacrylate) microgel (SAM), polydopamine (PDA), and sulfobetaine-modified polyethyleneimine (PES). The SAMs were used to construct controllable morphology by using the PDA combined with PES (PDAS) as the intermediate layer, which can be easily modulated via adjusting the crosslinking degree and contents of SAMs. The obtained SAM/PDAS coatings exhibit high anti-protein adhesive properties and can effectively inhibit the adhesion of cells, bacteria, and platelet through the synergy of high deposition density and controllable morphology. In addition, the stability of SAM/PDAS coating is improved owing to the anchoring effects of PDAS to substrate and SAMs. Importantly, the ex vivo blood circulation test in rabbits suggests that the SAM/PDAS coating can effectively decrease thrombosis without anticoagulants. This study provides a versatile coating method to address the integration of zwitterionic microgel-based coatings with high deposition density and controllable morphology onto various substrates for wide biomedical device applications. Statement of significance Thrombosis is a major cause of medical device implantation failure, which results in significant morbidity and mortality. In this study, inspired by natural biological surfaces (fish skin and vascular endothelial layer) and the anchoring ability of mussels, we report a convenient and efficient method to firmly anchor zwitterionic microgels using an oxidative co-deposition strategy. The prepared coating has excellent antifouling and antithrombotic properties through the synergistic effect of physical morphology and chemical composition. This biomimetic surface engineering strategy is expected to provide new insights into the clinical problems of blood-contacting devices related to thrombosis.

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CURRENT CANCER DRUG TARGETS · 2023 ·Vol. 23 ·期 6 ·471-481 · IF 3

Receptor Type Protein Tyrosine Phosphatase Epsilon (PTPRE) Plays an Oncogenic Role in Thyroid Carcinoma by Activating the AKT and ERK1/2 Signaling Pathway

Peng Chen,Zhang Chunming,Yu Wenjie,Li Le,Zhang Zhen,Liu Ting,Zhang Yan,Fan Gaiping,Huangfu Hui

Background: Thyroid carcinoma (TC) is a common malignant tumor in human and its incidence has been increasing in recent years. Studies have shown that receptor type protein tyrosine phosphatase epsilon (PTPRE) is a key regulator of tumorigenesis in cancer progression, but its role in TC has not been revealed. Objective: Here, in this work, we explored the essential role of PTPRE in TC progression. Methods: The expression of PTPRE in TC clinical samples and cell lines was detected by RT-qPCR and Western blot. Cell proliferation was measured by MTT and cell cycle analysis. Cell migration, invasion and epithelial-mesenchymal transition (EMT) were analyzed by wound healing, transwell, and immunofluorescent staining assays. AKT and ERK1/2 signaling pathway related protein level was analyzed by Western blot. Results: PTPRE was highly expressed in TC clinical samples and cell lines, especially anaplastic thyroid carcinoma (ATC). High level of PTPRE was associated with tumor size and TNM stage. Upregulated PTPRE promoted cell proliferation, and enhanced the migration, invasion and EMT of TC cells, whereas the knockdown of PTPRE suppressed these behaviors. Importantly, we confirmed that the AKT and ERK1/2 signaling pathways were activated by PTPRE, reflected by the enhanced protein level of phosphorylated AKT and ERK1/2. Conclusion: Accordingly, we indicated that PTPRE plays an oncogenic role in TC progression via activating the AKT and ERK1/2 signaling pathway. These findings indicated that modulation of PTPRE expression may as a potential strategy to interfere with the progression of TC.

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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Intelligent Biomimetic Nanoplatform for Systemic Treatment of Metastatic Triple-Negative Breast Cancer via Enhanced EGFR-Targeted Therapy and Immunotherapy

Xiaoxi Wang,Xueqin Zhu,Bingyu Li,Xiuyu Wei,Yalan Chen,Yun Zhang,Yan Wang,Wenyan Zhang,Sijia Liu,Zimai Liu,Wenjie Zhai,Pingping Zhu,Yanfeng Gao,Zhenzhen Chen

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, and it is associated with a high recurrence rate, metastatic potential, and poor prognosis. Thus, effective therapeutic strategies for TNBC are urgently required. The epidermal growth factor receptor (EGFR) is considered to be a potential therapeutic target for TNBC. However, there are limitations to the use of targeted therapies, such as afatinib (AFT), particularly drug resistance. Here, we investigated a poly(d,l-lactide-glycolide) (PLGA)-based intelligent bionic nanoplatform, termed AFT/2-BP@PLGA@MD, which combined targeted therapy with immunotherapy. In this platform, PLGA was used to encapsulate 2-bromo-palmitate (2-BP), a palmitoylation inhibitor, to enhance the efficacy of AFT against TNBC cells. PLGA was coated with a cancer cell membrane anchored with a cleavable peptide by matrix metalloproteinase-2 to block programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1). 2-BP significantly enhanced the capacity of AFT to inhibit the proliferation and migration of tumor cells in vitro. Moreover, the tumor cell membrane-coated AFT/2-BP@PLGA@MD nanoparticles exhibited enhanced tumor targeting ability in vivo. The AFT/2-BP@PLGA@MD nanoparticles significantly inhibited the growth and metastasis of 4T1 tumor and prolonged the survival of tumor-bearing mice. The nanoparticles also triggered antitumor immune response. Collectively, we report an effective therapeutic strategy for clinically refractory TNBC.

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LANGMUIR · 2016 · IF 3.993

Superior Catalytic Performance of Gold Nanoparticles Within Small Cross-Linked Lysozyme Crystals

Mingyue Liu,Libing Wang,Renliang Huang,Yanjun Yu,Rongxin Su,Wei Qi,Zhimin He

Bionanomaterials synthesized by bioinspired templating methods have emerged as a novel class of composite materials with varied applications in catalysis, detection, drug delivery, and biomedicine. In this study, two kinds of cross-linked lysozyme crystals (CLLCs) with different sizes were applied for the in situ growth of Au nanoparticles (AuNPs). The resulting composite materials were characterized by light microscopy, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy. The catalytic properties of the prepared materials were examined in the catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). It was found that the size of the AuNPs increased with an increase in Au loading for both small and large crystals. In addition, small crystals favored homogeneous adsorption and distribution of the metal precursors. And the size of the AuNPs within small crystals could be maintained below 2.5 nm by managing the HAuCl4/lysozyme molar ratio. Furthermore, the lysozyme functional groups blocked the AuNP activity sites, therefore reducing their catalytic activity. This effect was more pronounced for small AuNPs. Moreover, the mass transfer of reactants (4-NP) from solution to AuNPs within the crystals restricted their catalytic reduction, leading to superior catalytic performance of the AuNPs within small cross-linked lysozyme crystals (Au@S-CLLCs) compared to those within large cross-linked lysozyme crystals (Au@L-CLLCs) at similar Au loadings. Finally, an increase in Au loading clogged the crystal channels with increased quantities of larger AuNPs, thus impeding the catalytic performance of Au@S-CLLCs.

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NEW JOURNAL OF CHEMISTRY · 2012 ·Vol. 36 ·期 10 ·1985-1991 · IF 2.605

MicroRNA-21 detection based on molecular switching by amperometry

Yunlei Zhou,Zhaoyan Zhang,Zhenning Xu,Huanshun Yin,Shiyun Ai

A sensitive and selective electrochemical method for microRNA-21 (miRNA-21) detection was developed. This detection tactic was based on graphene, gold nanoparticles (AuNPs), locked nucleic acid (LNA) incorporated hairpin DNA switching and enzymatic signal amplification. Graphene and AuNPs can improve the electrode conductivity and increase the electrode active surface. The LNA incorporated hairpin DNA probe was modified with biotin at its 5′-end and –SH at its 3′-end. After the probe hybridized with target miRNA-21, its loop-and-stem structure was unfolded to force the biotin away from the electrode surface. Through the specific interaction between biotin and streptavidin-horseradish peroxidase (streptavidin-HRP), miRNA-21 can be quantitatively realized by electrochemical detection of the enzymatic product of benzoquinone in the presence of hydrogen peroxide and hydroquinone. The determination conditions, such as probe concentration, probe immobilization time, hybridization time and applied potential, were optimized. This assay allowed the detection of miRNA-21 in the range of 1–5000 pM with a detection limit of 0.4 pM (S/N = 3). Based on the locked nucleic acid incorporated probe with hairpin structure, the sensor can well discriminated complementary and base mismatched sequences. Successful attempts were made in miRNA-21 expression analysis of human HeLa cells and normal human hepatic L02 cells.

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RSC Advances · 2019 ·Vol. 9 ·期 10 ·5338-5346 · IF 3.049

Modification of 3D printed PCL scaffolds by PVAc and HA to enhance cytocompatibility and osteogenesis

Jingqi Ma,Lili Lin,Yi Zuo,Qin Zou,Xin Ren,Jidong Li,Yubao Li

In the study, a specific material system that contains poly-(ε-caprolactone) (PCL), polyvinyl acetate (PVAc) and hydroxyapatite (HA) was used to fabricate porous scaffolds employing a 3D printing technique for bone regeneration. Four groups of 3D printing scaffolds were fabricated: PCL, PCL/PVAc, PCL/HA and PCL/PVAc/HA for comparision. The morphologies, mechanical properties and biological characteristics of these scaffolds were analyzed using SEM, a material testing machine, in vitro cell culture and in vivo animal experiments. The results showed that these 3D printed scaffolds possessed porous channel structures with a hole size of 375–475 μm and porosity of 74.1–76.1%. The compressive moduli of the scaffolds increased with the addition of HA and decreased with the addition of PVAc. The PCL/PVAc/HA scaffold exhibited higher cell proliferation and bone formation rates than other groups (p < 0.001), which could be attributed to the synergistic effect of PAVc and HA components. Two types of new bone formation patterns in the scaffold were found in this study: one is the new bone formed directly on the grid matrix, and the other is the new bone initially formed in the center of the scaffold channel and then remolded to concentric circles. The osteogenesis pattern of the latter is analogous to the osteon structure of a cortical bone. The 3D printed scaffold based on PCL/PVAc/HA tri-component system is a promising prospect for future individualized bone repair applications.

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Bioengineered · 2022 · IF 6.832

Cleavage stimulation factor 2 promotes malignant progression of liver hepatocellular carcinoma by activating phosphatidylinositol 3′-kinase/protein kinase B/mammalian target of rapamycin pathway

Meng-Hui Zhang,Jun Liu

Liver hepatocellular carcinoma (LIHC) is the most common type, comprising 75–85% of all liver malignancies. We investigated the roles of cleavage stimulation factor 2 (CSTF2) in LIHC and explored the underlying mechanisms. CSTF2 expression and its association with LIHC patient survival probability were analyzed with The Cancer Genome Atlas. CSTF2 expression in LIHC cells was assessed using western blot and quantitative real-time PCR. Alterations in CSTF2 expression were induced by cell transfection. Cell colony formation, apoptosis, proliferation, invasion, and migration were assessed using colony formation, flow cytometry, 5-ethynyl-2ʹ-deoxyuridine, and transwell assays. Pathway enrichment analysis was performed using gene set enrichment analysis (GSEA). The expression of apoptosis-, metastasis-, and pathway-associated factors was determined via western blot. The pathway rescue assay was further performed using 740Y-P or Wortmannin. CSTF2 upregulation was observed in LIHC tissues and cells. Patients with high CSTF2 expression had a lower probability of overall survival. CSTF2 overexpression enhanced colony formation, proliferation, invasion and migration, while repressing apoptosis in LIHC cells. GSEA revealed that CSTF2 was mainly enriched in the phosphatidylinositol 3′-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Western blot analysis proved that CSTF2 overexpression activated this pathway. CSTF2 knockdown yielded the opposite effects. 740Y-P, a PI3K activator, reversed the CSTF2 knockdown-triggered effects on cell proliferation, apoptosis, invasion, and migration. Moreover, Wortmannin, a PI3K inhibitor, also reversed the CSTF2 overexpression-induced effects on cell proliferation, apoptosis, invasion, and migration. These results indicated that CSTF2 overexpression might exacerbate the malignant phenotypes of LIHC cells via activation of PI3K/AKT/mTOR pathway.

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ACS Biomaterials Science & Engineering · 2020 · IF 4.152

Controlled Delivery of Growth Factor by Hierarchical Nanostructured Core–Shell Nanofibers for the Efficient Repair of Critical-Sized Rat Calvarial Defect

Chunpeng Huang,Guang Yang,Shaobing Zhou,En Luo,Jian Pan,Chongyun Bao,Xian Liu

Electrospun nanofibers have received much attention as bone tissue-engineered scaffolds for their capacity to mimic the structure of natural extracellular matrix (ECM). Most studies have reproduced nanofibers with smooth surface for tissue engineering. This is quite different from the triple-helical nanotopography of natural collagen nanofibrils. In this study, hierarchical nanostructures were coated on the surface of drug-loaded core–shell nanofibers to mimic natural collagen nanofibrils. The nanoshish-kebab (SK) structure was decorated regularly on the surface of the nanofibers, and the inner-loaded bone morphogenetic protein 2 (BMP2) exhibited a gentle release pattern, similar to a zero-order release pattern in kinetics. The in vitro study also showed that the SK structure could accelerate cell proliferation, attachment, and osteogenic differentiation. Four groups of scaffolds were implanted in vivo to repair critical-sized rat calvarial defects: (1) PCL/PVA (control); (2) SK-PCL/PVA; (3) PCL/PVA-BMP2; and (4) SK-PCL/PVA-BMP2. Much more bone was formed in the SK-PCL/PVA group (24.57 ± 3.81%) than in the control group (1.21 ± 0.23%). The BMP2-loaded core–shell nanofibers with nanopatterned structure (SK-PCL/PVA-BMP2) displayed the best repair efficacy (76.38 ± 4.13%), followed by the PCL/PVA-BMP2 group (39.86 ± 5.74%). It was believed that the hierarchical nanostructured core–shell nanofibers could promote osteogeneration and that the SK structure showed synergistic ability with nanofiber-loaded BMP2 in vivo for bone regeneration. Thus, this BMP2-loaded core–shell nanofiber scaffold with hierarchical nanostructure holds great potential for bone tissue engineering applications.

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