Acta Biomaterialia
·
2021
·
IF 8.947
Wenjun Lu,Sha Wang,Rui Liu,Ying Guan,Yongjun Zhang
Depletion of human serum albumin (HSA), the most abundant protein in human plasma , from serum/plasma is a prerequisite before their proteomic analysis. Molecularly imprinted polymers (MIPs) using HSA as a template have been designed for this purpose, but suffer from a low sorption capacity and low selectivity. Here, a new HSA-imprinted polymer was synthesized using N-isopropylacrylamide (NIPAM) as the main monomer ; acrylamide (AAm), methacrylic acid (MAA), and dimethylaminoethyl methacrylate (DMAEMA) as functional monomers; and oligoglutamic acid-based peptide crosslinker (PC) as a crosslinker at pH 5.5. When pH is adjusted to 7.4, the peptide chains in the polymer change from a helical conformation to an extended coil conformation, and the polymer swells. Consequently, the template protein is removed completely. When pH is adjusted back to 5.5, the peptide chains fold back precisely to the helical conformation. Both the size and shape of the imprint cavities are restored. Therefore, the polymer rebinds the template protein selectively. Highest imprinting factor (IF) was observed at pH 5.5 at which the polymer was synthesized. The IF increases with the increasing number of glutamic acid residues in the PCs because of their increased degree of helicity at pH 5.5. No improvement in imprinting effect was observed when using a peptide crosslinker containing both L- and D-glutamic acid residues and hence incapable of folding into α-helix, further confirming the key role of the pH-induced helix-coil transition of the peptide chains. The MIP synthesized here presents a much higher affinity to HSA than the nontemplate proteins. It could be used repeatedly without evident decrease in sorption capacity. Because of the mild eluting conditions, the secondary structure of the extracted HSA protein remains unchanged. Finally, the MIP was used to deplete HSA from human serum. Because of its high sorption capacity and high selectivity, HSA was depleted completely and selectively. Statement of significance A new molecularly imprinted polymer (MIP) using human serum albumin (HSA) as a template was synthesized using N-isopropylacrylamide (NIPAM) as the main monomer; acrylamide (AAm), methacrylic acid (MAA), and dimethylaminoethyl methacrylate (DMAEMA) as functional monomers; and oligoglutamic acid-based peptide crosslinker as a crosslinker. Because of the reversible and precise pH-induced helix-coil transition of the peptide chains, the template protein was removed facilely and completely under mild conditions. Simultaneously, a significant improvement in imprinting efficiency was obtained. The sorption capacity was as high as 648.05 mg/g and the imprinting factor was 7.9. Because of its high selectivity and high binding capacity, the MIP synthesized here is highly promising for the depletion of HSA, the most abundant protein in serum, which is a prerequisite for its proteomic analysis. For the first time, complete and selective depletion of HSA from human serum was achieved using a protein-imprinted polymer.
研究领域:
生物材料
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蛋白质组学
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高分子科学
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分析化学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 8
·3692-3704
·
IF 5.396
Shufen Wu,Yue Sun,Di Chen,Huanhuan Liu,Zhenjing Li,Mianhua Chen,Changlu Wang,Lei Cheng,Qingbin Guo,Xin Peng
Monascin (MS) and ankaflavin (AK), as typical yellow lipid-soluble pigments identified from Monascus-fermented products, have been confirmed to possess diverse biological activities such as anti-oxidation, reversing diabetes, and anti-atherosclerosis, and have received increasing attention in recent years. Certainly Monascus-fermented product with a high content of MS/AK is also a concern. The current work explored interactions between MS/AK and human serum albumin (HSA) as well as their influence on the anti-oxidant properties of MS/AK. Moreover, the anti-glycation potential of Monascus-fermented products rich in MS and AK (denoted as Mps) was assessed. The results showed that the fluorescence emission of HSA was quenched by MS/AK through a static quenching mechanism, and MS–HSA and AK–HSA complexes were mainly formed by van der Waals forces and hydrophobic interactions, but AK showed a higher binding affinity than MS. Although the DPPH radical-scavenging abilities of MS–HSA and AK–HSA complexes declined, Mps significantly reduced the formation of fructosamine, α-dicarbonyl compounds and advanced glycation end products (AGEs) in the in vitro glycation model (HSA–glucose). Notably, approximately 80% of fluorescent-AGEs were suppressed by Mps at a concentration of 0.95 mg mL−1, while aminoguanidine (AG, a reference standard) caused only 65% decrease at the same concentration. Although radical scavenging and metal chelating activities could justify the observed anti-glycation activity of Mps, in-depth research on the structures of other functional compounds present in Mps except MS/AK and reaction mechanisms should be performed. Overall, the present study proved that Mps would be promising sources of food-based anti-glycation agents because of their superior inhibitory effect on AGEs.
研究领域:
食品科学
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生物化学
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药理学
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DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Hao Wu,Xuefeng Ding,Yun Chen,Yanfei Cai,Zhaoqi Yang,Jian Jin
Antibody–drug conjugates (ADC) are an inevitable trend in the development of modern “precision medicine”. The goal of this work is to produce enzyme-responsive antibody nanoparticle-loaded medication (FMSN-Dox-H2-AE01) based on the EGFR antibody (AE01) and human serum albumin (HSA) shelled mesoporous silica nanoparticles. HSA and antibodies on the surface of the particlescan not only enhance the biocompatibility of the particle and avoid early drug leakage but also allow selective biodegradation triggered by matrix metalloproteinase-2 (MMP-2), which are overexpressed enzymes in some tumor tissues. The cytotoxicity test confirmed favorable safety and efficacy of the ADC. The mortality rate of cancer cells is about 85–90%. Moreover, the antibody nanoparticle-loaded drug showed distinguishing controlled release efficiency toward cancer cells induced by different levels of MMP-2 and pH. This enzyme-responsive FMSN-Dox-H2-AE01 offers a promising option for cancer therapy.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2019
·
IF 5.256
Yu Cai,Ji-Cheng Niu,Yu-Qi Liu,Xin-Li Du,Zhi-Yong Wu
Paper-based analytical device (PAD) has received more and more attention in the field of point-of-care test (POCT) due to its low cost, portability and simple operation. Sensitivity and selectivity are two important aspects in clinical diagnostic analysis. However, low sensitivity of a PAD limits its wider application for POCT. Here we introduced a PAD that can clean and enrich the protein content from salty media with both electric field (E) and pH gradient (double E/pH gradients), with which 100-fold enrichment effect could be achieved within 70 s as demonstrated by fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) from artificial urine media. With post staining of the protein stacking band with bromophenol blue (BPB), selective colorimetric detection of human serum albumin (HSA) was achieved simply with smartphone camera in the clinically significant range of 10–300 mg‧L −1 (R 2 = 0.99) with a limit of detection (LOD) of 4.9 mg‧L −1 . Detection of microalbuminuria (MAU) of diabetic patients was demonstrated with this method without difference (ɑ = 0.01) to that by the clinical method (immunoturbidimetry). This work demonstrated the potential of this PAD method in online sample pretreatment and detection of target component from complex physiological samples.
研究领域:
分析化学
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生物医学工程
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临床诊断
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Lei Ouyang,Ling Yao,Rongmei Tang,Xiangliang Yang,Lihua Zhu
The concentration of bilirubin in serum is a key indicator for liver function, because excess bilirubin accumulation may lead to serious health problems like Jaundice. It is known that in comparison with total bilirubin, the concentration of hydrophobic free bilirubin is more closely associated with Jaundice because of its capability to cross the capillary walls and even blood-brain barrier. However, it is not easy to detect the low concentration of free bilirubin (∼ nM) in the presence of large amount of protein-bound bilirubin (> 150 μM), and no point-of-care detection tool is available. In the present work, direct detection of free bilirubin was realized by using surface enhanced Raman spectroscopy (SERS). By mimicking the in vivo chemical interaction between glucuronic acid and bilirubin, glucose functionalized Au nanoparticles were synthesized for selective capture and detection of free bilirubin. By developing a convenient detection procedure of using robust Au array chip and internal standard calibration method, the sensitive detection of free bilirubin with detection limit down to 0.1 nM was achieved on a handhold Raman spectrometer by monitoring its fingerprint spectra. The clinical applicability was demonstrated with analyzing the spiked and real blood samples. As a proof of concept, the binding constant between bilirubin and human serum albumin (HSA) was determined with the present method. The influence of the binding capacity of the HSA for bilirubin in the presence of competing molecule salicylate sodium was also quantitatively measured, which demonstrated the importance of detection of free bilirubin instead of total bilirubin for warning the risk of bilirubin encephalopathy.
研究领域:
分析化学
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生物医学工程
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纳米技术
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临床诊断
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光谱学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Yunfei Lian,Fenyan Feng,Xinwang Meng,Yue Hu,Meirong Huo,Guangji Wang,Juan Li
Integration of multi-modal imaging techniques and various cancer treatments based on their respective characteristics would be beneficial for enhancing anticancer efficacy. Exploiting an “all-in-one” nanoparticle with high biocompatibility has attracted widespread attention. Herein, two clinically proven modalities, human serum albumin (HSA) and indocyanine green (ICG), were selected to create HSA-stable barium sulfonate nanoparticles (HSA@ICG–Ba) through the reaction of a sulfonic acid group with barium ions. Our nano-probe showed excellent optical properties and X-ray absorption capacity, which can be applied in tumor theranostics. Utilizing the rich tumor accumulation of HSA@ICG–Ba, this nanoparticle can obtain multifaceted tumor information through fluorescence (FL), computerized tomography (CT), photoacoustic (PA) imaging, and single photon emission computed tomography (SPECT) imaging. Additionally, radiation sensitization therapy and photothermal therapy based on HSA@ICG–Ba were evaluated using both in vitro and in vivo models. The efficacy of tumor radiotherapy can be further improved by mild hyperthermia owing to the relieved tumor hypoxia. Finally, the favorable safety profile of HSA@ICG–Ba is confirmed by blood index analysis and tissue section observation. Therefore, this study explored an “all-in-one” barium sulfonate nanoparticle with high biocompatibility for FL/CT/PA/SPECT imaging-guided synergetic photothermal-radiotherapy of tumors, providing a new approach and potential pathway for tumor theranostics.
研究领域:
生物医学工程
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纳米技术
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癌症治疗
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医学成像
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE BIOLOGY
·
2016
·Vol. 249
·期 6
·757-767
·
IF 1.991
Lai Lu,Li Ya-Ping,Mei Ping,Chen Wu,Jiang Feng-Lei,Liu Yi
The mitochondrial toxicity induced by GSH-CdTe Quantum dots (QDs) of different sizes was investigated. The decreases in absorbance and transmission electron microscopy images show that QDs induce the swelling of mitochondria. Results of flow cytometry indicate that QDs cause a reduction of mitochondrial membrane potential (MMP). A remarkable increase in fluidity of protein regions of mitochondrial membrane is observed, whereas the lipid regions are not obviously affected. Cyclosporin A (CsA) effectively prevents the QD-induced mitochondrial swelling. On the basis of these results, it is proposed that QDs induce mitochondrial permeability transition (MPT). Moreover, with increasing QDs size, a pronounced MPT is observed. The difference between the membrane fluidity induced by QDs and Cadmium ion and the ineffective protective effects of EDTA suggests that the mitochondrial toxicity of QDs cannot be only attributed to the release of metal ion. The protective effects of HSA indicate that the interaction of QDs with pore-forming protein gives rise to the increase in membrane fluidity. This hypothesis is demonstrated by the interaction of QDs with model membranes and proteins using differential scanning calorimetry and isothermal titration microcalorimetry. In conclusion, as the size of QDs increases, the binding affinity of QDs with membrane protein increases, and therefore causes a pronounced mitochondrial damage.
研究领域:
纳米技术
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毒理学
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细胞生物学
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生物物理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Weicai Wang,Yuanyuan Wang,Minghui Ma,Hyung Jong Jin,Xuemei Li
The construction of completely biocompatible and biodegradable tumor suppressors by a simple and reliable method is essential for the clinical application of cancer-targeted drugs. Herein, by inserting glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) into human serum albumin (HSA) assembly molecules, we constructed a cancer-targeted cascade bioreactor for synergistic starvation and photodynamic therapy (PDT). The modification of HSA could block the GOx activity and reduce the cytotoxicity of normal cells and organs. Through active targeting and passive enhanced permeability and retention effect, the loading of AS1411 could promote the cascade bioreactors to effectively target nucleolin-overexpressed tumors. Once internalized by cancer cells, as a result of catalyzing hydrogen peroxide (H2O2) to produce oxygen (O2), the protein nano-cascade reactor promoted microenvironmental oxygenation, which would subsequently lead to an increase in cytotoxic singlet oxygen (1O2) production under light irradiation as well as the decomposition of intracellular glucose. In vitro and in vivo studies showed that the cascaded nanoreactors could significantly enhance therapeutic efficacy through synergistic starvation therapy and enhanced PDT as well as chemotherapy. This cascade strategy will be demonstrated in clinical applications with huge potential.
研究领域:
癌症研究
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纳米技术
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生物医学工程
·
药学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 17
·1903341
·
IF 15.84
Qing You,Kaiyue Zhang,Jingyi Liu,Changliang Liu,Huayi Wang,Mengting Wang,Siyuan Ye,Houqian Gao,Letian Lv,Chen Wang,Ling Zhu,Yanlian Yang
Multifunctional nanoplatforms for imaging-guided synergistic antitumor treatment are highly desirable in biomedical applications. However, anticancer treatment is largely affected by the pre-existing hypoxic tumor microenvironment (TME), which not only causes the resistance of the tumors to photodynamic therapy (PDT), but also promotes tumorigenesis and tumor progression. Here, a continuous O 2 self-enriched nanoplatform is constructed for multimodal imaging-guided synergistic phototherapy based on octahedral gold nanoshells (GNSs), which are constructed by a more facile and straightforward one-step method using platinum (Pt) nanozyme-decorated metal–organic frameworks (MOF) as the inner template. The Pt-decorated MOF@GNSs (PtMGs) are further functionalized with human serum albumin-chelated gadolinium (HSA-Gd, HGd) and loaded with indocyanine green (ICG) (ICG-PtMGs@HGd) to achieve a synergistic PDT/PTT effect and fluorescence (FL)/multispectral optoacoustic tomography (MSOT)/X-ray computed tomography (CT)/magnetic resonance (MR) imaging. The Pt-decorated nanoplatform endows remarkable catalase-like behavior and facilitates the continuous decomposition of the endogenous H 2 O 2 into O 2 to enhance the PDT effect under hypoxic TME. HSA modification enhances the biocompatibility and tumor-targeting ability of the nanocomposites. This TME-responsive and O 2 self-supplement nanoparticle holds great potential as a multifunctional theranostic nanoplatform for the multimodal imaging-guided synergistic phototherapy of solid tumors.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
医学成像
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）