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ADVANCED MATERIALS · 2024 · IF 27.4

Transcytosable and Ultrasound-Activated Liposome Enables Deep Penetration of Biofilm for Surgical Site Infection Management

Guowei Wang,Chengyue Zhang,Zixuan Huang,Jifan Chen,Hongjian Chen,Tao Lin,Zhuxian Zhou,Ning Gu,Pintong Huang

Biofilm-associated surgical site infection (BSSI) is a common and grievous postoperative complication lacking effective remedies, mainly due to the poor drug accumulation and penetration in the biofilms featured by dense extracellular polymeric substances (EPSs). Here, it is found that the vascular cell adhesion molecule-1 (VCAM1) is highly overexpressed in the vascular cells of BSSI. It is proposed that the combination of VCAM1-mediated transcytosis and ultrasonic cavitation can consecutively overcome the biological barriers of vascular endothelial cells and EPS for biofilm eradication. To demonstrate the feasibility, a VCAM1-targeted and ultrasound (US)-activated liposome (LPCOTML) loaded with a reactive-oxygen-species (ROS)-responsive lipoid prodrug of oleoyl meropenem, sonosensitizer of lipoid Ce6, and perfluoropentane is developed. LPCOTML can recognize the receptors on vascular cells, and initiate receptor-mediated transcytosis for transendothelial transport into the BSSI periphery. LPCOTML subsequently transforms from nanoparticle into microbubble via liquid–gas phase transition under US irradiation, triggering strong ultrasonic cavitation to blow up the EPS and deeply penetrate the biofilms. The sonosensitizer Ce6 induces ROS production under US irradiation and triggers the release of meropenem to induce potent antibacterial effect in a BSSI model. This study presents an effective strategy to tackle the biological barriers in BSSI via combining receptor-mediated transcytosis and ultrasonic cavitation.

研究领域: 医学 · 药剂学 · 感染性疾病
✓ 已验证 DOI PubMed 高影响因子
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American Journal of Translational Research · 2021 · IF 4.06

The construction of multifunctional nanoparticles system for dual-modal imaging and arteriosclerosis targeted therapy

Pengda Qiu,Yunhong Xu

Atherosclerosis is a major risk factor for the development of cardiovascular disease. Unfortunately, due to relatively low sensitivities and poor resolution, the results of surgical resection are often largely unsatisfactory. Moreover, many chemotherapeutic agents, such as curcumin (Cur), are restricted by the low blood-brain barrier (BBB) permeability. Recently, nanotechnology proposes new opportunities to overcome these treatment barriers. In this study, superparamagnetic iron oxide nanoparticles (SPIO) was prepared by the high-temperature solid-state method, and then loaded into amphiphilic polymer DSPE-PEG to form SDP nanoparticles by hydrogen bonding in oil phase. The curcumin was encapsulated in SDP nanoparticles by self-assembly. Finally, vascular cell adhesion molecule-1 (VCAM-1) and Cy5.5 were conjugated on into SDP/Cur nanoparticles by amidation reaction. The average particle size of the prepared multifunctional SDP-VCAM-1/Cur/Cy5.5 nanoparticles is 124.4 nm, which can provide the sustained release of Cur. Moreover, the nanoparticles are proved to have superparamagnetic properties and fluorescence properties. In vitro cell experiments show that nanoparticles have excellent biocompatibility, blood compatibility and macrophage targeting. These results show that SDP-VCAM-1/Cur/Cy5.5 nanoparticles can be used not only as dual imaging probe for magnetic resonance (MR) and fluorescence imaging, but also as carriers to deliver chemotherapeutic drugs to inflammatory tissue, thus providing a promising opportunity for the treatment, molecular imaging and targeted therapy in atherosclerosis due to their established specificity and safety.

研究领域: 医学影像学 · 纳米医学 · 药剂学
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

Preparation and application of EpCAM electrochemiluminescent aptamer sensor based on porous UiO-66(Ce) loading CdTe/CdS quantum dots

Yanqing Ran,Rui Dai,Xiaoshuo Zhang,Faqiong Zhao,Baizhao Zeng

Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein and its detection is important for diagnosis and therapeutic prognostic assessment of many cancers. Herein, a highly sensitive electrochemiluminescence (ECL) sensor was developed for its detection. In the ECL sensor, dimercaptosuccinic acid-capped core/shell structured CdTe/CdS quantum dot (QD) was loaded on metal-organic framework material UiO-66(Ce) as electrochemical luminophore; Ti 3 C 2 /Ag composite was introduced for immobilizing EpCAM aptamer. Due to the well immobilization of QD and catalysis of UiO-66(Ce), the obtained luminophore CdTe/CdS QDs@UiO-66(Ce) displayed a strong and stable ECL signal. Furthermore, the Ti 3 C 2 /Ag could act as a co-reactant accelerator to boost the ECL signal. Thus, the resulted sensor had quite strong initial ECL signal for signal-off detection. Further experiment showed that it exhibited good linear response to EpCAM over the concentration range of 1 pg mL −1 − 10 ng mL −1 in pH 7.4 Tris buffer, with a detection limit low to 0.66 pg mL −1 . Additionally, the ECL sensor also presented high selectivity and satisfying reproducibility; its practicability was demonstrated by the successful determination of EpCAM in serum samples.

研究领域: 分析化学 · 生物化学 · 癌症研究 · 纳米技术
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Frontiers in Oncology · 2021 · IF 6.244

Disulfiram Alone Functions as a Radiosensitizer for Pancreatic Cancer Both In Vitro and In Vivo

Xu Ying,Lu Lunjie,Luo Judong,Wang Lili,Zhang Qi,Cao Jianping,Jiao Yang

The prognosis of pancreatic cancer remains very poor worldwide, partly due to the lack of specificity of early symptoms and innate resistance to chemo-/radiotherapy. Disulfiram (DSF), an anti-alcoholism drug widely used in the clinic, has been known for decades for its antitumor effects when simultaneously applied with copper ions, including pancreatic cancer. However, controversy still exists in the context of the antitumor effects of DSF alone in pancreatic cancer and related mechanisms, especially in its potential roles as a sensitizer for cancer radiotherapy. In the present study, we focused on whether and how DSF could facilitate ionizing radiation (IR) to eliminate pancreatic cancer. DSF alone significantly suppressed the survival of pancreatic cancer cells after exposure to IR, both in vitro and in vivo. Additionally, DSF treatment alone caused DNA double-strand breaks (DSBs) and further enhanced IR-induced DSBs in pancreatic cancer cells. In addition, DSF alone boosted IR-induced cell cycle G2/M phase arrest and apoptosis in pancreatic cancer exposed to IR. RNA sequencing and bioinformatics analysis results suggested that DSF could trigger cell adhesion molecule (CAM) signaling, which might be involved in its function in regulating the radiosensitivity of pancreatic cancer cells. In conclusion, we suggest that DSF alone may function as a radiosensitizer for pancreatic cancer, probably by regulating IR-induced DNA damage, cell cycle arrest and apoptosis, at least partially through the CAM signaling pathway.

研究领域: 肿瘤学 · 药理学 · 放射生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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Brain and Behavior · 2022 ·Vol. 12 ·期 5 ·e2558 · IF 3.405

Artemisinin upregulates neural cell adhesion molecule L1 to attenuate neurological deficits after intracerebral hemorrhage in mice

Jianjiang Wang,Jie Yin,Xi Zheng

Background and purpose Intracerebral hemorrhage (ICH) is a subtype of stroke and results in neurological deficits in patients without any effective treatments. Artemisinin (ART), a well-known antimalarial Chinese medicine, exerts multiple essential roles in the central and peripheral nervous system due to its antioxidative and anti-inflammation properties. Neural cell adhesion molecule L1 (L1CAM, L1) is considered to be implicated in neural development, functional maintenance, and neuroprotection during disease. However, whether these two essential molecules are neuroprotective in ICH remains unclear. Methods Therefore, the present study investigated the influence of ART on the recovery of neurological deficits in a mouse model of ICH induced by collagenase and the underlying mechanism. Results It was revealed that ART is capable of upregulating L1 expression to alleviate brain edema, reduce oxidative stress, and inhibit inflammation to alleviate ICH-induced brain injury to improve the neurological outcome in mice suffering from ICH. Conclusion These results may lay the foundation for ART to be a novel candidate treatment for ICH.

CAS / MDL: 314-13-6
研究领域: 神经科学 · 药理学 · 分子生物学 · 神经病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nanomedicine · 2018 · IF 5.005

Dual targeting delivery of miR-328 by functionalized mesoporous silica nanoparticles for colorectal cancer therapy

Yang Li,Yanhong Duo,Peng Zhai,Lisheng He,Keli Zhong,Yue Zhang,Kaibin Huang,Jinfeng Luo,Han Zhang,Xiaofang Yu

Aim: We aim to explore the regulatory mechanism of miR-328 and further develop miR-328-loaded mesoporous silica nanoparticles (MSNs) and surface-decorated with polymerized dopamine, epithelial cell adhesion molecule aptamer and bevacizumab for the dual-targeting treatment of colorectal cancer (CRC). Materials & methods: The relationship between miR-328 and CPTP and the mechanism and antitumor effect of MSNs-miR-328@PDA-PEG-Apt-Bev were evaluated. Results: We found CPTP is a direct target of miR-328. Compared with other groups, MSNs-miR-328@PDA-PEG-Apt-Bev can significantly increase the level of miR-328 and inhibit the expression of CPTP in SW480 cells. The results exhibit this multifunctional bioconjugates can achieve an increased binding ability and much higher cytotoxicity to CRC both in vitro and in vivo. Conclusion: This multifunctional nanoplatform is a promising miRNA replacement therapy for CRC.

研究领域: 纳米技术 · 肿瘤学 · 分子生物学 · 药学
✓ 已验证 DOI PubMed 高影响因子
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Cell Communication and Signaling · 2025 ·Vol. 23 ·期 1 ·1-21 · IF 8.9

β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury

Li Lei,Peng Ruilong,Wang Cong,Chen Xin,Gheyret Dilmurat,Guan Siyu,Chen Bo,Liu Yafan,Liu Xilei,Cao Yiyao,Han Cha,Xiong Jianhua,Li Fanjian,Lu Taoyuan,Jia Haoran,Li Kaiji,Wang Jinchao,Zhang Xu,Xu Jianye,Wang Yajuan,Xu Xin,Li Tuo,Zhang Jianning,Zhang Shu

Neutrophils are the first responders among peripheral immune cells to infiltrate the central nervous system following a traumatic brain injury (TBI), triggering neuroinflammation that can exacerbate secondary tissue damage. The precise molecular controls that dictate the inflammatory behavior of neutrophils post-TBI, however, remain largely elusive. Our comprehensive analysis of the molecular landscape surrounding the trauma in TBI mice has revealed a significant alteration in the abundance of β2 integrin (ITGB2), predominantly expressed by neutrophils and closely associated with immune responses. Using the fluid percussion injury (FPI) mouse model, we investigated the therapeutic efficacy of Rovelizumab, an agent that blocks ITGB2. The treatment has demonstrated significant improvements in neurologic function in TBI mice, attenuating blood–brain barrier permeability, mitigating oxidative stress and inflammatory mediator release, and enhancing cerebral perfusion. Moreover, ITGB2 blockade has effectively limited the adherence, migration, and infiltration of neutrophils, and has impeded the formation of neutrophil extracellular traps (NETs) upon their activation. Finally, it was demonstrated that ITGB2 mediates these effects mainly through its interaction with intercellular adhesion molecule-1 (ICAM 1) of endotheliocyte. These findings collectively illuminate ITGB2 as a crucial molecular switch that governs the adverse effects of neutrophils post-TBI and could be targeted to improve clinical outcome in patients.

CAS / MDL: 75-12-7
研究领域: 神经科学 · 免疫学 · 创伤医学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOSENSORS & BIOELECTRONICS · 2020 · IF 10.257

A strategy for construction of highly sensitive glycosyl imprinted electrochemical sensor based on sandwich-like multiple signal enhancement and determination of neural cell adhesion molecule

Xionghui Ma,Mengxi Li,Peihong Tong,Chengjun Zhao,Jianping Li,Guobao Xu

A novel electrochemical sensor for a neural cell adhesion molecule (CD56) was constructed by glycosyl imprinting. A sandwich-like multi-signal generation strategy was first proposed in glycosyl imprinting sensors via boric acid affinity. Glycosyl-imprinted polymers were formed by electro-polymerization with poly-sialic acid (PolySia) as a template molecule and p -aminobenzeneboronic ( p -ABA) acid as a functional monomer . Methods such as scanning electron microscope (SEM), Fourier transform infrared spectrum (FT-IR), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) were used to characterize the successful formation of imprinted membranes. Confirmed by both simulation calculation and experimental results, a signal-amplified effect based on macromolecules was introduced for the first time. After re-absorption, aminobenzene borate was linked to the surface of the sensor by boric acid affinity due to the rich hexadoxyl structure of the CD56-terminal chain as a signal probe . Under optimal conditions, the detection limit of the sensor is as low as 0.47 ng/L, and it can be successfully applied to the detection of CD56 in human serum.

研究领域: 分析化学 · 生物化学 · 电化学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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Nano Today · 2023 · IF 17.4

Hybrid stem cell-derived bioresponsive vesicles for effective inflamed blood-brain barrier targeting delivery

Honghui Wu,Xinchi Jiang,Yaosheng Li,Yunfei Dong,Juanjuan Zheng,Lu Li,Ying Li,Jinqiang Wang,Xianming Lin,Xiangnan Zhang,Tianyuan Zhang,Zhen Gu,Jianqing Gao

Blood-brain barrier (BBB) dis-integrity, a characteristic of extensive inflammatory encephalopathy, provides the access for brain-targeted drug delivery. Inspired from the bioresponsiveness of stem cell, we conceived of new nano-scale delivery strategy via neural stem cell membrane-derived bioresponsive vesicles (NSC-Lipo) for inflamed BBB target delivery. After recombination of neural stem cell membranes with simple liposomes , the functional ligands, especially very late antigen-4 (VLA-4), were entirely engrafted into NSC-Lipo and equipped the NSC-Lipo with “pass order” to the “selective gate”. It bestowed the bioresponsive vesicles with selective target the injured brain microvessel endothelial cells (BMECs) and penetrate into the lesion through the vascular cell adhesion molecule-1 (VCAM-1)/VLA-4 interaction in the post-ischemic mice model. The released anti-inflammatory agent, metformin , could reverse the inflammatory response of BMECs and rapidly recovers BBB’s integrity. With the repair of BBB’s integrity and down regulation of VCAM-1 expression, the targeting ability of bioresponsive vesicles cease to be in force as well. The bioresponsive vesicles led to enhanced survival rate of ischemic stroke mice (from 30 % to 90 %) after just a single injection compared to metformin loaded bare liposomes.

CAS / MDL: 69-09-0 128446-36-6
研究领域: 神经科学 · 药剂学 · 干细胞生物学 · 药物递送系统
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

Supplementation of 3′-Sialyllactose During the Growth Period Improves Learning and Memory Development in Mice

Liuying Zhu,Minghui Wang,Hongyan Li,Ting Luo,Zeyuan Deng,Jing Li,Liufeng Zheng,Bing Zhang

3′-Sialyllactose (3′-SL), a major acidic oligosaccharide found in human milk, has been investigated to improve cognitive-enhancing effects with 3 weeks old C57BL/6 mice by administering 3′-SL orally at a dose of 350 mg/kg/day for 6 weeks. Behavioral tests indicated that supplementation with 3′-SL promoted cognitive and memory development in young mice. Through interaction network and coenrichment analysis, nine differentially expressed genes (DEGs) related to memory and cognition were identified and localized in the hippocampal tissue of mice. The intervention of 3′-SL significantly increased the metabolism of sialic acid in mouse hippocampal tissue and promoted the expression of learning-related genes (p < 0.05). Notably, it increased the expression of genes associated with neural cell adhesion molecule (NCAM, p < 0.05), glutamate receptors, and fibroblast growth factor receptor (FGFR, p < 0.05). This suggests that 3′-SL may elevate polysialylated NCAM (PSA-NCAM) levels, which could subsequently interact with FGFR and glutamate receptors, thereby enhancing synaptic growth and plasticity. Additionally, 3′-SL altered the composition of the mouse intestinal microbiota. The synergistic action of gut microbiota and intestinal sialidase promoted the production of free sialic acid, providing essential nutritional elements for the development of the brain’s nervous system. In conclusion, our findings provide new insights into the promoting effect of 3′-SL on cognitive development in growing mice and elucidate its molecular mechanisms.

研究领域: 神经科学 · 分子生物学 · 营养科学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Mesenchymal Stem Cell-Based Biomimetic Liposome for Targeted Treatment of Rheumatoid Arthritis

Lan Ma,Honghui Wu,Jian Cao,Nan Zhang,Yaosheng Li,Juanjuan Zheng,Xinchi Jiang,Jianqing Gao

Rheumatoid arthritis (RA) is a systemic autoimmune disorder that severely compromises joint health. The primary therapeutic strategy for advanced RA aims to inhibit joint inflammation. However, the nonspecific distribution of pharmacological agents has limited therapeutic efficacy and heightens the risks associated with RA treatment. To address this issue, we developed mesenchymal stem cell (MSC)-based biomimetic liposomes, termed MSCsome, which were composed of a fusion between MSC membranes and liposomes. MSC some with relatively simple preparation method effectively enhanced the targeting efficiency of drug to diseased joints. Interaction between lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 enhanced the affinity of the MSCsome for polarized macrophages, thereby improving its targeting capability to affected joints. The effective targeted delivery facilitated drug accumulation in joints, resulting in the significant inhibition of the inflammation, as well as protection and repair of the cartilage. In conclusion, this study introduced MSCsome as a promising approach for the effective treatment of advanced RA, providing a novel perspective on targeted drug delivery therapy for inflammatory diseases.

CAS / MDL: 97281-47-5
研究领域: 药理学 · 免疫学 · 生物技术 · 干细胞研究 · 药物递送系统
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2014 · IF 3.552

Carboxybetaine methacrylate oligomer modified nylon for circulating tumor cells capture

Chaoqun Dong,Huiyu Wang,Zhuo Zhang,Tao Zhang,Baorui Liu

Circulating tumor cells (CTC) capture is one of the most effective approaches in diagnosis and treatment of cancers in the field of personalized cancer medicine. In our study, zwitterionic carboxybetaine methacrylate (CBMA) oligomers were grafted onto nylon via atomic transfer random polymerization (ATRP) which would serve as a novel material for the development of convenient CTC capture interventional medical devices. The chemical, physical and biological properties of pristine and modified nylon surfaces were assessed by Fourier transform infrared spectra, atomic force microscope, water contact angle measurements, X-ray photoelectron spectroscopy, protein adsorption, platelet adhesion, and plasma recalcification time (PRT) determinations, etc. The results, including the significant decrease of proteins adsorption and platelets adhesion, as well as prolonged PRTs demonstrated the extraordinary biocompatibility and blood compatibility of the modified surface. Furthermore, we showed that upon immobilization of anti-epithelial cell adhesion molecular (anti-EpCAM) antibody onto the CBMA moiety, the modified nylon surface can selectively capture EpCAM positive tumor cells from blood with high efficiency, indicating the potential of the modified nylon in the manufacture of convenient interventional CTC capture medical devices.

研究领域: 生物医学工程 · 癌症研究 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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