COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
Hui Peng,Jia-Hui Wang,Feng Guo,Fang-Fang Zhu,Zu-Jun Wen,Hai-Jun Zhong,De-Sheng Liang
M2 tumor-associated macrophages (TAMs) play a pivotal role in cancer progression and therapy resistance. Inhibition of TAMs is of great significance to reshape the protumor environment to benefit therapeutic outcomes. In this work, we developed a novel TAMs and tumor cells dual-targeting nanoparticle (AT pep -NPs) system for cancer chemotherapy by integrating a docetaxel (DTX)-loaded nanocarrier and a multi-function peptide AT pep , which is composed of a phagocytosis-stimulating peptide-tuftsin (T pep ) fused with a substrate peptide-alanine-alanine-asparagine (AAN) of endoprotease legumain . In vitro protelytic and cellular uptake assays confirmed AT pep -NPs can be responsively activated into T pep -NPs by cleavage of legumain that is overexpressed in both tumor cells and TAMs, which then promoted tumor cells internalization and TAMs phagocytosis through neuropilin-1/Fc receptor pathways. Due to AAN deactivation effect, AT pep -NPs can effectively decrease the T pep -induced non-specific uptake by M1-polarized and normal macrophage during systemic circulation. Our results of in vivo experiments demonstrated AT pep -NPs outperformed T pep -NPs in tumor and TAMs dual-targeting delivery efficiency with markedly enhanced efficacy against both tumor growth inhibition and TAMs depletion. Overall, this study offers a novel approach for development of multitargeted delivery vehicle for improved cancer chemotherapy.
研究领域:
药理学
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肿瘤学
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纳米技术
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
TALANTA
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2024
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IF 5.6
Heng Zhang,Bin Luo,Ke Liu,Cheng Wang,Peichen Hou,Chunjiang Zhao,Aixue Li
Palmitic acid (PA) is a kind of saturated high fatty acid, which is involved in physiological safety and food quality. A surface molecularly imprinted polymer (MIP) electrochemical sensor was prepared on MXene surface using dopamine (DA) as functional monomer. The electrode was modified with gold nanoparticles (AuNPs), ferrocene-graphene oxide-multiwalled carbon nanotubes (Fc-GO-MWCNT) composite to enhance the electroactive area and conductivity. The sensor was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), electrochemical impedance spectroscopy (EIS) and Differential pulse voltammetry (DPV), respectively. The parameters concerning this assay and various regeneration conditions have been carefully studied. The sensor can detect PA in the range of 1 nM-1 mM (R 2 = 0.995), the limit of detection (LOD) is 0.48 nM (S/N = 3), and the limit of quantification (LOQ) is 1.61 nM. The artificial neural network (ANN) model in machine learning is further used to analyze the data collected by the sensor. The results show that the back propagation (BP) neural network in ANN is more suitable for the intelligent analysis of PA. The practicality of the sensor was confirmed by detecting PA in pork samples. This is the first MIP-based electrochemical sensor for PA, and it has great potential in practical applications.
研究领域:
分析化学
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电化学
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机器学习
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食品科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2022
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IF 16.874
Jianhua He,Wenli Zhang,Xiaoju Zhou,Fengfei Xu,Jiahui Zou,Qiqi Zhang,Yi Zhao,Hongliang He,Hu Yang,Jianping Liu
Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis; however, the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells. Here, we report reactive oxygen species (ROS)-responsive and size-reducible nanoassemblies, formed by multivalent host-guest interactions between β-cyclodextrins (β-CD)-anchored discoidal recombinant high-density lipoprotein (NP 3 ST ) and hyaluronic acid-ferrocene (HA-Fc) conjugates. The HA-Fc/NP 3 ST nanoassemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP 3 ST , allowing for further plaque penetration, macrophage-targeted cholesterol efflux and drug delivery. In vivo pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP 3 ST reduces plaque size by 53%, plaque lipid deposition by 63%, plaque macrophage content by 62% and local inflammatory factor level by 64% compared to the saline group. Meanwhile, HA-Fc/NP 3 ST alleviates systemic inflammation characterized by reduced serum inflammatory factor levels. Collectively, HA-Fc/NP 3 ST nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability, thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.
研究领域:
纳米技术
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药学
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心血管疾病
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2021
·Vol. 12
·期 1
·1-14
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IF 14.919
Jiang Cheng-Tao,Chen Kai-Ge,Liu An,Huang Hua,Fan Ya-Nan,Zhao Dong-Kun,Ye Qian-Ni,Zhang Hou-Bing,Xu Cong-Fei,Shen Song,Xiong Meng-Hua,Du Jin-Zhi,Yang Xian-Zhu,Wang Jun
Modulating effector immune cells via monoclonal antibodies (mAbs) and facilitating the co-engagement of T cells and tumor cells via chimeric antigen receptor- T cells or bispecific T cell-engaging antibodies are two typical cancer immunotherapy approaches. We speculated that immobilizing two types of mAbs against effector cells and tumor cells on a single nanoparticle could integrate the functions of these two approaches, as the engineered formulation (immunomodulating nano-adaptor, imNA) could potentially associate with both cells and bridge them together like an ‘adaptor’ while maintaining the immunomodulatory properties of the parental mAbs. However, existing mAbs-immobilization strategies mainly rely on a chemical reaction, a process that is rough and difficult to control. Here, we build up a versatile antibody immobilization platform by conjugating anti-IgG (Fc specific) antibody (αFc) onto the nanoparticle surface (αFc-NP), and confirm that αFc-NP could conveniently and efficiently immobilize two types of mAbs through Fc-specific noncovalent interactions to form imNAs. Finally, we validate the superiority of imNAs over the mixture of parental mAbs in T cell-, natural killer cell- and macrophage-mediated antitumor immune responses in multiple murine tumor models.
研究领域:
癌症免疫疗法
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2024
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IF 8.5
Mengyan Wang,Ying Li,Chi Zhang,Gaiping Li,Lina Zou
A sensitive signal-on photoelectrochemical aptasensor for antibiotic determination was constructed based on the energy level matching between ferrocene and CuInS 2 . P-type CuInS 2 microflower was complexed with reduced graphene oxide (CuInS 2 /rGO) to get photocathode current with good photoelectric conversion efficiency and stability. Then, hairpin DNA (HP) was covalently bonded to the electrode surface. A triple helix DNA (THMS) was used as a molecular switch. After the specific recognition between target and THMS in homogeneous solution, ferrocene labeled probe (Fc-T2) was released. Finally, Fc-T2 was captured by the HP, which leaded the obvious increase of photocurrent for the energy level matching between ferrocene and CuInS 2 . The increase of the photocurrent signal was proportional to the concentration of target amoxicillin (AMOX), the linear range was 100 fM-100 nM with detection limit of 19.57 fM. Meanwhile, the method has been successfully applied for milk and lake water samples analysis with satisfactory results.
研究领域:
分析化学
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生物化学
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环境科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2019
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IF 6.393
Xiaoqing Zhao,Jing Wang,Hou Chen,Hui Xu,Liangjiu Bai,Wenxiang Wang,Huawei Yang,Donglei Wei,Baiqing Yuan
A novel electrochemical immunoassay platform for multi-signal amplification has been constructed and applied to the simultaneous detection of three tumor markers (TMs). The platform was successfully developed by polyethyleneimine (PEI)-polydopamine (PDA)/reduced graphene oxide (rGO) nanocomposites. PDA/rGO as the substrates can simultaneously load with detection antibodies (Ab 2 ) and large amounts of PEI, which PEI were further used to immobilize different signal labels. Three TMs of carcinoembryonic antigen (CEA), prostate specific antigen (PSA) and alpha fetoprotein (AFP) were employed as potential factors. Ferrocenecarboxylic acid (Fc), anthraquinone-2-carboxylic acid (Aq) and acetylsalicylic acid (ASA) were employed as distinguishable signal labels. Electrochemical responses of designed sandwich-type immunosensor were successfully investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The multiplexed immunoassay displayed excellent linear response in the range of 0.102 pg/mL–112 ng/mL for CEA and PSA, 0.117 pg/mL–117 ng/mL for AFP. The detection limit of three TMs were 91 fg/mL, 101 fg/mL and 83 fg/mL for CEA, PSA and AFP, respectively. Moreover, this electrochemical immunoassay platform exhibited excellent reproducibility, sensitivity and selectivity for the simultaneous detection of multiple biomarkers.
研究领域:
生物医学工程
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分析化学
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纳米技术
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电化学
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生物传感器
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Xia Liu,Jingyi Niu,Jiwei Shen,Huiyuan Chu,Chaozhan Wang,Yinmao Wei
Adsorbents modified with small molecular ligands have shown great advantages in the downstream purification of antibody, but they still face some challenges caused by single-site adsorption mechanism. Taking the advantage of hydrophobic binding site and sugar chain in Fc region of antibody molecular, a Y-type ligand-modified adsorbent with two-site synergistic adsorption towards antibody was created by integrating 5-aminobenzimidazole and 3-aminophenylboronic acid on the molecular backbone of triazine bonded on the surface of agarose gel. Using dissociation constant and adsorption capacity as indicators, the interaction between immunoglobulin G (IgG) and the adsorbent was probed by comparison with three control adsorbents and by changing pH, salt concentration, and competitive agents in buffer. All the obtained indicators imply a boronate affinity and hydrophobic charge induction synergistic effect imposed on IgG by the benzimidazole and boric acid group in the Y-type ligand, enabling the adsorbent to provide a stronger affinity (Kd = 4.31×10 −6 M), larger adsorption capacity (Qm = 187 mg/g) and more excellent selectivity for IgG over the adsorbents with single-site adsorption mechanism. This is further demonstrated by selectively isolating IgG from protein mixture and serum. Also, pH is confirmed as an important factor for improving the synergistic effect and adsorption selectivity of the adsorbent. Under optimal condition, IgG was successfully separated from human serum and monoclonal antibody (mAb) from cell culture supernatant, with purities of 94.9 % and 97.5 % and recoveries of 94.3 % and 96.8 %, respectively. The results are comparable to those with protein A adsorbent, suggesting a good application potential of the adsorbent in the separation of antibody drugs.
研究领域:
生物化学
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生物技术
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药学
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化学工程
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2020
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IF 10.652
Xiaoyu Xu,Zishan Zeng,Jie Chen,Binyao Huang,Zilin Guan,Yanjuan Huang,Zeqian Huang,Chunshun Zhao
Utilizing intratumoral iron mediated Fenton reaction to induce cancer cells destruction, chemodynamic therapy (CDT) is an emerging tumor-specific therapeutic strategy. However, the CDT efficacy is severely restrained by insufficient endogenous H 2 O 2 and catalytic ferrous ions in tumor site. Herein, based on innovative small molecule prodrug design concept, an acid-labile ferrocene-modified cinnamaldehyde prodrug (Fc-CA) was first synthesized. Skillfully combining ROS-generator CA with Fenton catalyst Fc in its molecular structure, Fc-CA could synchronously elevate H 2 O 2 level and catalytic iron amount for enhanced CDT efficacy. Then, hydrophobic Fc-CA was efficiently encapsulated into hydrophilic cyclodextrin-modified hyaluronic acid conjugate (HA-CD) via host-guest interactions, to spontaneously form pH/redox dual-responsive supramolecular catalytic nanoreactor (HA-CD/Fc-CA NPs). The nanoreactor with high drug loading and stability, excellent catalytic activity and tumor specificity could preferentially accumulate in tumor tissues via EPR effect and CD44 receptor-mediated internalization. Through the cleavage of acid-labile hydrazone bond under acidic lysosome environments, the nanoreactor would be dissociated and release pre-protected CA for reinforced oxidation therapy and amplified H 2 O 2 level, which would in turn react with Fc through cascaded Fenton reaction, to generate highly cytotoxic •OH for enhanced cancer killing in a positive feedback process. Both in vitro and in vivo results verified excellent cascade-amplifying therapeutic performance and favorable biocompatibility of this nanoreactor. This study provides an innovative strategy for exploiting versatile organic therapeutic nanoplatforms, simultaneously activating tumor-specific oxidative stress amplification and cascaded enhanced Fenton reaction for superior cancer therapy with excellent biosafety.
研究领域:
纳米技术
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癌症治疗
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化学生物学
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材料科学
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药学
✓ 已验证
产品关联
DOI
高影响因子