SENSORS AND ACTUATORS B-CHEMICAL
·
2023
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IF 8.4
Wenjing Huang,Li Wang,Hao Zhang,Zhihao Han,Yueqing Gu
The incidence of prostate cancer has increased rapidly in recent years. And the detection of tumor markers is an effective way for early diagnosis and poor prognosis. Prostate cancer is associated with growth factor receptors. Epidermal growth factor receptor (EGFR) expression is increased in a majority of prostate cancer patients. Peptide probes have the advantages of convenient modification and selective and rapid clearance in the molecular imaging of tumors. H1 is a short peptide designed and modified based on the CDR3 region of a nanobody targeting the epidermal growth factor receptor (EGFR) with high affinity for malignant tumors that overexpress EGFR. The CDR3 sequence of nanobodies has a long finger-like structure that allows deep interaction with the cryptic epitope of the antigen. Here we synthesized a sensitive fluorescent peptide probe of H1 conjugated to imaging moieties MPA. Experimental data showed that H1-MPA targets EGFR with high affinity. Meanwhile, H1-MPA has high tumor uptake and a strong signal-to-noise ratio. In addition, the near-infrared fluorescent probe H1-MPA can determine tumor boundaries and can be used to monitor and prevent tumor metastasis, including hepatic metastasis, for accurate tumor diagnosis. H1-MPA provides a promising tool for cancer diagnosis.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Jingmou Yu,Liangliang Wang,Yun Ling,Xin Xiao,Juntao Gong,Hongguang Jin,Jing Xu,Pu Chen,Xin Xie,Lei Zhang
Triple-negative breast cancer is an offensive tumor that is highly challenging to cure. In this study, we developed novel polymeric nanoparticles that target dual receptors and respond to reducing conditions for chemotherapeutic drug release in the treatment of triple-negative breast cancer. Then we synthesized and characterized a targeted peptide-grafted chondroitin sulfate A-ss-deoxycholic acid (TCSSD) copolymer and prepare doxorubicin (DOX)-loaded TCSSD (TCSSD-D) micelles high-loading content. The bioresponsive drug release of TCSSD-D nanoparticles was demonstrated in a glutathione-containing phosphate buffer solution . We found that TCSSD-D effectively targeted CD44 and P-selectin receptors both in vitro and in vivo . TCSSD-D micelles were higher cytotoxicity and cellular uptake than unmodified DOX-containing micelles in MDA-MB-231 cells. Furthermore, TCSSD-D micelles showed the strongest suppression of tumor growth among three DOX-based formulations in triple-negative MDA-MB-231-bearing nude mice . These results suggest that amphiphilic TCSSD nanoparticles can serve as a targeted and intelligent delivery vehicle for triple-negative breast cancer therapy.
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Bioactive Materials
·
2023
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IF 18.9
Zhenhao Zhao,Chufeng Li,Yiwen Zhang,Chao Li,Yongchao Chu,Xuwen Li,Peixin Liu,Hongyi Chen,Yu Wang,Boyu Su,Qinjun Chen,Tao Sun,Chen Jiang
A long-standing paucity of effective therapies results in the poor outcomes of triple-negative breast cancer brain metastases. Immunotherapy has made progress in the treatment of tumors, but limited by the non-immunogenicity of tumors and strong immunosuppressive environment, patients with TNBC brain metastases have not yet benefited from immunotherapy. Dual immunoregulatory strategies with enhanced immune activation and reversal of the immunosuppressive microenvironment provide new therapeutic options for patients. Here, we propose a cocktail-like therapeutic strategy of microenvironment regulation-chemotherapy-immune synergistic sensitization and construct reduction-sensitive immune microenvironment regulation nanomaterials ( [email protected] ). [email protected] modified with targeting peptide penetrates the BBB and is subsequently internalized into metastatic breast cancer cells, releasing silybin and oxaliplatin responsively in the cells. [email protected] preferentially accumulates at the metastatic site and can significantly prolong the survival period of model animals. Mechanistic studies have shown that [email protected] can effectively induce immunogenic cell death of metastatic cells, activate immune responses and increase infiltration of CD8 + T cells. Meanwhile, the activation of STAT3 in the metastatic foci is attenuated and the immunosuppressive microenvironment is reversed. This study demonstrates that [email protected] with dual immunomodulatory functions provides a promising immune synergistic therapy strategy for breast cancer brain metastases.
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Chemosensors
·
2023
·Vol. 11
·期 6
·330
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IF 4.2
Mengjiao Mo,Haoyi Yuan,Jingyu Zhang,Jian Wang,Ying Liu,Juanjuan Peng,Lingzhi Zhao
Antibiotic contamination has become a serious global problem due to abuse and misuse. Therefore, it is important to develop an efficient detection method to monitor the rational use of antibiotics. In this study, fluorescent gold nanoclusters with 11-mercaptoundecanoic acid as ligands (MUA-AuNCs) were synthesized by a one-step method firstly. Rare earth ions (Re3+) can enhance the fluorescence of MUA-AuNCs through inducing the aggregation of MUA-AuNCs, but antibiotics decrease the fluorescence of the Re3+-MUA-AuNCs to different degrees through coordination with Re3+and competitive absorption with AuNCs. Therefore, a sensor array was obtained on the basis of the above mechanism, which can detect and discriminate six different antibiotics with a detection range from 40 to 300 μM. A 100% correct classification was achieved. The fluorescent sensor array showed high selectivity for tetracycline antibiotics and good anti-interference performance was demonstrated. Combined with pattern recognition methods, the proposed sensor array can be used for the discrimination of different antibiotics and binary antibiotic mixtures. Furthermore, the excellent performance of this sensor array in quantitation and blind sample recognition further validates its potential for practical applications.Keywords:antibiotics;sensor array;gold nanoclusters;rare earth ions
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2022
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IF 9.965
Hongyan Cui,Ming Zhang,Liuwei Zhang,Haidong Li,Yue Wang,Yan Zhao,Qixian Chen,Jingyun Wang
Proteins have been appreciated to be a superlative modality of therapeutics in view of their direct roles in regulating diverse sets of biological events, nonetheless, the clinical applications of the proteinic therapeutics have been strictly limited to act on the cell surface receptors owing to their inherent cell-impermeable character of the proteins. To this obstacle, we contrived carboxylation reaction upon the proteins (RNase A) into the overall negatively charged pro-RNase, followed by elaboration of intelligent pH-responsive pro-RNase delivery nanocolloids based on co-precipitation of pro-RNase and Arg-Gly-Asp (RGD)-functionalized poly(ethylene glycol) (PEG)- block -polyanion with aids of inorganic calcium phosphate (CaP). The resulting nanocolloids appeared to actively accumulate into glioma due to the specific binding affinities of RGD and glioma-enriched α V β 3 and α V β 5 integrins. Furthermore, the pH responsiveness to the acidic endolysosomal microenvironment of all compositions of nanocolloids (including: decarboxylation of pro-RNase composition to restore the native RNase A, ionization of CaP composition to elicit osmotic pressure , and charge reversal of PEG- block -polyanion into membrane-disruptive polycation) could stimulate not only efficient endolysosomal escape for translocation into the cytosol but also structural disassembly for ready liberation of the RNase A payloads, eventually exerting non-specific RNA degradation for apoptosis of the affected cells. Systemic dosage of the proposed nanocolloids demonstrated potent anti-tumor efficacies towards xenograft glioma due to massive RNA degradation. Therefore, our proposed RNase A prodrug nanocolloids could represent as a versatile platform for engineering transcellular protein delivery systems, which are expected to spur thriving emergence of a spectrum of proteins in precision intervention of intractable diseases.
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Biointerphases
·
2022
·Vol. 17
·期 6
·
IF 1.916
Wang Li,Cui Baocheng,Qiu Keyuan,Huang Jiao,Liang Changhai
Nitrile hydratase (NHase, EC 4.2.1.84) is an excellent biocatalyst that catalyzes the hydration of nitrile substances to their corresponding amides. Given its catalytic specificity and eco-friendliness, NHase has extensive applications in the chemical, pharmaceutical, and cosmetic industries. To improve the affinity between Rhodococcus erythropolis CCM2595-derived NHase ( Re NHase) and adiponitrile, this study used a semirational design to improve the efficiency of Re NHase in catalyzing the generation of 5-cyanopentanamide from adiponitrile. Enzyme kinetics analysis showed that Km of the mutant Re NHase B:G196Y was 3.265 mmol l −1 , which was lower than that of the wild-type NHase. The affinity of the mutant Re NHase B:G196Y to adiponitrile was increased by 36.35%, and the efficiency of the mutant Re NHase B:G196Y in catalyzing adiponitrile to 5-cyanopentamide was increased by 10.11%. The analysis of the enzyme-substrate interaction showed that the hydrogen bond length of the mutant Re NHase B:G196Y to adiponitrile was shortened by 0.59 Å, which enhanced the interaction between the mutant and adiponitrile and, thereby, increased the substrate affinity. Similarly, the structural analysis showed that the amino acid flexibility near the mutation site of Re NHase B:G196Y was increased, which enhanced the binding force between the enzyme and adiponitrile. Our work may provide a new theoretical basis for the modification of substrate affinity of NHase and increase the possibility of industrial applications of the enzyme.
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Food Bioscience
·
2023
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IF 5.2
Jingwen Zhu,Xue Xia,Foxin Zhang,Shiqing Song,Heping Cui,Khizar Hayat,Qiang Zhang,Xiaoming Zhang,Chi-Tang Ho
Light color and savory flavor are difficult to be integrated in ‘Thermal Process Flavoring’ through traditional Maillard reaction . A light-colored seasoning from gluten peptide-glucose system was prepared through gradient temperature-elevating Maillard reaction with extra-added l -cysteine. Greater saltiness and umami enhancement effect of Maillard reaction products (MRPs) were observed from weaker reaction, while lower temperature and longer heating time were conducive to yield kokumi-taste compounds. With the addition of l -cysteine, intensities of fluorescence and UV-VIS absorption of MRPs were weakened. An inhibition of browning and a decrease of α-dicarbonyls concentration caused by l -cysteine were observed. The addition of l -cysteine also led to an increase of peptides below 500 Da (from 53.27 mg/mL to 56.50 mg/mL) and a decrease of cross-linking products in 1–3 kDa, which accounted for superior umami and gentle kokumi attribute of the light-colored products compared with the MRPs without l -cysteine addition.
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REACTIVE & FUNCTIONAL POLYMERS
·
2022
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IF 4.966
Xiao Li Li,Peng Liu,Bin Chu,Jin Mei He,Zhen Wang,Song Wang,Chang Sheng Chen,Xiao Hong Ge,Hui Li,Wei Qiang Liu
Myocardial infarction (MI) is a common heart emergency that potentially causes death. Injectable hydrogels with excellent malleability and filling properties are suitable for myocardial injection and can avoid the need for open surgery. In this study, dopamine grafted hyaluronic acid (HADOPA) was synthesized and combined with sodium alginate (Alg) and Ca 2+ -loaded liposomes (Ca-FVI) to prepare a series of injectable thermosensitive sodium hyaluronate/sodium alginate hydrogels (HADOPA/Ca-FVI/Alg). At 37 °C, the HADOPA/Ca-FVI/Alg solution rapidly changed from liquid to hydrogel because of the crosslinking between sodium alginate and the Ca 2+ released from Ca-FVI at a phase transition time of 100–200 s. The HADOPA/Ca-FVI/Alg scaffolds exhibited a porous 3D network structure, controlled porosity, and connected pore properties. Increasing the proportion of HADOPA increases the elasticity and absorbance of hydrogels. Experimental assessment showed that the hydrogels have good biocompatibility and that Alg1-HADOPA is more conducive to the adhesion, proliferation, and spreading of mouse cardiac myocytes while maintaining the best cell state. These findings suggest that HADOPA/Ca-FVI/Alg hydrogels improve cell proliferation and tissue repair, and that they are a promising therapeutic option for cardiac repair after MI.
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PHYTOMEDICINE
·
2022
·
IF 6.656
Feng-Jie Liu,Xu-Yan Chen,Jiao Yang,Zhen Zhao,Qiao-Lei Wang,Ping Li,Yan Jiang,Hui-Jun Li
Background Fritillariae Bulbus (FB) is widely used as a traditional medicine for the treatment of lung meridian diseases. It has been proved that FB has good anti-non-small cell lung cancer (NSCLC) activity. However, the active components and potential mechanism are still not clear. Purpose To reveal the bioactive components of FB against NSCLC and potential mechanism through spectrum-effect relationship and proteomics. Method First, the FB extract was chemically profiled by UHPLC-QTOF-MS and the inhibitory effect of FB extract on A549 cell viability was evaluated by Cell Counting Kit-8 assay. Second, orthogonal-partial least squares-regression analysis was applied to screen potential active compounds through correlating the chemical profile with corresponding inhibitory effect. Third, the anti-NSCLC activities of potential active components were further investigated in terms of cell proliferation, cell cycle and cell apoptosis in vitro and tumor growth in vivo . Finally, proteomics was utilized to reveal the underlying anti-NSCLC mechanism. Results Six potential active components including verticine, verticinone, zhebeirine, ebeiedinone, yibeissine and peimisine were screened out by spectrum-effect relationship. Among them, zhebeirine showed higher inhibitory effect on A549 cell viability with IC 50 value of 36.93 μM and dosage-dependent inhibition of A549 xenograft tumor growth in nude mice. Proteomics and western blotting assays indicated that zhebeirine could arrest cell cycle by down-regulating the expressions of CDK1, CDK2, Cyclin A2, Cyclin B2 and inhibiting the phosphorylation of p53. Moreover, the proteins participating in p53 signaling pathway including PCNA, 14–3–3σ, CHEK1 were significantly decreased, which suggested that zhebeirine affected cell cycle progression through p53 signaling pathway. Conclusion This study not only provides scientific evidence to support the clinical application of FB against NSCLC, but also demonstrates that zhebeirine is a promising anti-NSCLC lead compound deserving further studies.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2023
·
IF 4.4
Yulin Wang,Libo Nie,Yongbiao Hua,Liang Gong,Xiuzhen Qiu,Huishi Guo
In this work, a ratiometric fluorometric sensor based on nickel nanoclusters (NiNCs)-europium complex (NiNCs-Eu 3+ ) was constructed for the highly selectivity detection of tetracyclines (TCs) in water samples. In the presence of TCs, the blue fluorescence of the sensor NiNCs-Eu 3+ was quenched at 430 nm and the characteristic red fluorescence of Eu 3+ -TCs appeared at 620 nm because of the combined help of inner filter effect (IFE) and antenna effect. Under the optimized conditions (100 mM Eu 3+ (100 µL); temperature (25℃); reaction time (10 min), HEPES buffer solution (pH = 7.0)), the sensor offered a wide detection range of tetracycline (TC) and oxytetracycline (OTC) from 0.1 to 50 μM with the detection limit (LOD) of 25 nM and 21 nM, respectively. Moreover, the sensor was able to detect of TC and OTC in tap and lake water with high recovery rate (89.10%-97.60%). In addition, the portable paper-based sensor was constructed using filter paper embedded with NiNCs-Eu 3+ . The distinct fluorescent color of the paper-based sensor varied from bright blue to red against different concentrations of TC and OTC. These above findings demonstrated the potential for wide application of as-prepared ratio metric fluorescence sensor for visual detection of TCs in water samples.
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ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Yi-Xuan Li,Junji Li,Hai-Bo Zeng,Xue-Ji Zhang,Serge Cosnier,Dan Shan
Constructing robust and efficient luminophores is of significant importance in the development of electrochemiluminescence (ECL) amplification strategies. Inspired by the resonance energy transfer in natural light-harvesting systems, we propose a novel ECL amplification system based on ECL resonance energy transfer (ECL-RET), which integrates two luminophores, benzimidazole (BIM) and zinc(II) tetrakis(4-carboxyphenyl)porphine (ZnTCPP), into one framework. Through disassembling and reconstruction processes, numerous BIM surround ZnTCPP in the constructed ZIF-9-ZnTCPP. Combined with the overlapped spectra between the emission of BIM and the absorption of ZnTCPP, the energy of multiple BIM (donor) can be concentrated to a single ZnTCPP (acceptor) to amplify the ECL emission of the acceptor. This work provides a convenient way to design an efficient ECL-RET system, which initiates a brand-new chapter in the development of ECL amplification strategies.
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ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Huahui Gao,Xinmei Song,Qirong Chen,Ruo Yuan,Yun Xiang
The demethylase of fat mass and obesity related protein (FTO) is critical to regulate the dynamic N 6 -methyladenosine (m6A) modification of eukaryotic mRNAs, and its overexpression has found to be closely related to the initiation of several cancers. On the basis of a target-promoted specific activation of DNAzyme strategy coupled with self-primer exponential amplification reaction (SPEXPAR) cycles and DNA supersandwich assemblies, the highly sensitive and label-free electrochemical FTO assay approach is established. The modification of the catalytic core nucleobase of the DNAzyme probe by m6A can inhibit its cleavage activity. The presence of target FTO catalyzes the elimination of the methyl group to restore the DNAzyme activity, which cleaves the hairpin substrates to trigger the SPEXPAR for yielding many ssDNAs. The capture of these DNAs on the sensor electrode leads to the initiation of supersandwich assembly formation of long dsDNAs . Tremendous electrochemical signal probe of [Ru(NH 3 ) 6 ]Cl 3 are then absorbed on these dsDNAs to produce highly amplified catalytic currents with the assistance of K 3 [Fe(CN) 6 ] for detecting trace FTO with 63.1 fM detection limit. Furthermore, the sensor can be employed for selective assay of FTO in cell lysates, revealing the great potential of this sensing strategy for biomedical and biological study applications.
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