RSC Advances
·
2022
·Vol. 12
·期 30
·19063-19071
·
IF 4.036
Yehong Liu,Miaoxin Chen,Gaoyang Li,Shouhong Xu,Honglai Liu
In this study, a pH/reduction dual responsive carrier containing 42nt-nucleic acid HApt based on mesoporous silica nanoparticles (MSNs) was designed. Two kinds of low molecular weight oligomeric hyaluronic acid (HA) were used to graft onto MSN for better drug encapsulation. Crosslinked MSN-HA3000gel and MSN-HA11000gel were prepared by crosslinking the HA chain through the sulfhydrylization of the carboxyl group on the HA side chain. An appropriate amount of sulfhydryl nucleic acid (HApt-SH) was added during the crosslinking reaction, which realized the targeting ability and apoptosis function to cancer cells overexpressing the HER2 receptor. Crosslinked HA had a good effect on decreasing the side effect of DOX that the drug leakage was less than 20% under a normal body environment. However, it could realize rapid and efficient drug release in a tumor environment. As to the release of HApt, it exhibited a good response to GSH. The cytotoxicity test showed that HApt contained in HAgel had a great targeting effect and significant cytotoxicity to SKBR3 cells. As a whole, this MSN-HAgel enabled the combination of gene therapy and chemotherapy, showing the synergistic effect of “1 + 1 > 2”, providing a novel idea for cancer treatments.
研究领域:
纳米技术
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药学
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癌症研究
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生物医学工程
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DOI
PubMed
高影响因子
Nanomaterials
·
2022
·Vol. 12
·期 4
·696
·
IF 5.719
Chao Zhang,Shuangqing Fu,Fanghua Zhang,Mengnan Han,Xuming Wang,Jie Du,Honglei Zhang,Wei Li
Combination chemotherapy is emerging as an important strategy for cancer treatment with decreased side effects. However, chemotherapeutic drugs with different solubility are not easy to realize co-delivery in traditional nanocarriers. Herein, an affibody modified G-quadruplex DNA micellar prodrug (affi-F/GQs) of hydrophilic 5-fluorodeoxyuridine (FUdR) by integrating polymeric FUdRs into DNA strands is developed for the first time. To achieve synergistic efficacy with hydrophobic drugs, curcumin (Cur) is co-loaded into affi-F/GQs micelles to prepare the dual drug-loaded DNA micelles ([email protected]/GQs), in which affibody is employed as a targeting moiety to facilitate HER2 receptor-mediated uptake.[email protected]/GQs have a small size of approximately 130 nm and exhibit excellent stability. The system co-delivers FUdR and Cur in a ratiometric manner, and the drug loading rates are 21.1% and 5.6%, respectively. Compared with the physical combination of FUdR and Cur,[email protected]/GQs show higher cytotoxicity and greater synergistic effect on HER2 positive gastric cancer N87 cells. Surprisingly,[email protected]/GQs significantly enhance the expression and activity of apoptosis-associated proteins in Bcl-2/Bax-caspase 8, 9-caspase 3 apoptotic pathway, which is the main factor in the death of tumor cells induced by FUdR. Overall, this nanoencapsulation is a promising candidate for the targeted co-delivery of drugs with significant differences in solubility.Keywords:G-quadruplex;DNA micelles;affibody;5-fluorodeoxyuridine;curcumin;synergetic therapy
研究领域:
癌症治疗
·
纳米技术
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2015
·Vol. 8
·期 16
·8553-8558
·
IF 7.394
Lin Fan,Yanyan Tian,Rong Yin,Doudou Lou,Xizhi Zhang,Meng Wang,Ming Ma,Shouhua Luo,Suyi Li,Ning Gu,Yu Zhang
Conventional immunohistochemistry is limited to subjective judgment based on human experience and thus it is clinically required to develop a quantitative immunohistochemical detection. 3,3′-Diaminobenzidin (DAB) aggregates, a type of staining product formed by conventional immunohistochemistry, were found to have a special optical property of dark-field imaging for the first time, and the mechanism was explored. On this basis, a novel immunohistochemical method based on dark-field imaging for detecting HER2 overexpressed in breast cancer was established, and the quantitative analysis standard and relevant software for measuring the scattering intensity was developed. In order to achieve a more sensitive detection, the HRP (horseradish peroxidase)-labeled secondary antibodies conjugated gold nanoparticles were constructed as nanoprobes to load more HRP enzymes, resulting in an enhanced DAB deposition as a dark-field label. Simultaneously, gold nanoparticles also act as a synergistically enhanced agent due to their mimicry of enzyme catalysis and dark-field scattering properties.
研究领域:
医学影像
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癌症研究
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Ying Li,Meiqi Qian,Yuping Cheng,Xue Qiu
In situ cell imaging plays a crucial role in studying physiological and pathological processes of cells. Proximity ligation assay (PLA) and rolling circle amplification (RCA) are commonly used to study the abundance and interactions of biological macromolecules. The most frequently applied strategy to visualize the RCA products is with single-fluorophore probe, however, cellular auto-fluorescence and unbound fluorescent probes could interfere with RCA products, leading to non-specific signals. Here, we present a novel approach combining aptamer mediated PLA, RCA, and Förster Resonance Energy Transfer (FRET), namely Apt-PLA-RCA-FRET, for sensitive in situ imaging and analysis of the abundances and interactions of membrane proteins such as tetraspanin CD63 and human epidermal growth factor receptor 2 (HER2). Apt-RCA-FRET was initially designed to show its ability to assess the abundance of target proteins on different cells. Dual functional oligonucleotides served as both the aptamer for recognizing specific membrane proteins and the primer of circular DNA for following RCA process, and the resulting RCA products were subsequently imaged by FRET signals from Cy3 to Cy5 probes which hybridized sequentially on them. FRET was demonstrated to show its great potential to resist the interferences of nonspecific fluorescence compared to single-fluorophore strategies. PLA was then introduced to Apt-RCA-FRET to investigate the spatial localization of different proteins on cell membrane and their interactions. Our approach utilizing aptamer as membrane proteins recognition element simply converted the abundance of proteins into nucleic acid signals and facilitated the following signal amplification, thus it serves as an important alternative to methods typically based on antibody and presents a more robust and sensitive method for analyzing the abundances of different cell membrane proteins and their spatial localization, which offers valuable insights into physiological and pathological processes of cells.
研究领域:
细胞生物学
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分子生物学
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生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Yang Bing,Liu Wenxu,Li Meiying,Mo Jingxin
Despite intensive research, ovarian cancer has the highest mortality rates among gynecological malignancies, partly because of its rapid acquisition of chemoresistance to platinum therapy. Hence, strategies are needed to effectively treat carboplatin-resistant ovarian cancer. In this study, we designed and prepared hyaluronic acid-decorated metal-organic frameworks for the targeted delivery of GSK-J1, a JMJD3 demethylase inhibitor (HA@MOF@GSK-J1) for the synergistic treatment of carboplatin-resistant ovarian cancer. HA@MOF@GSK-J1 showed outstanding effectiveness in the inhibition of ovarian cancer in vitro. Furthermore, HA@MOF@GSK-J1 demonstrated higher induction of apoptosis, reduced cell motility, and diminished cell spheroids by attenuating HER2 activity through the effectual activation of H3K27 methylation in its promoter area. Finally, our in vivo results confirmed that HA@MOF@GSK-J1 had better treatment efficacy for carboplatin-resistant ovarian tumor xenografts. Our results highlight the potential of HA@MOF@GSK-J1 as an effective strategy to improve the treatment of carboplatin-resistant ovarian cancer.
研究领域:
肿瘤学
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药学
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
Chemistry Africa-A Journal of the Tunisian Chemical Society
·
2026
·Vol. 9
·期 1
·36
·
IF 2.2
Mohsin Dheyaa Hussein,Ali Jassim Mohammed,Ahmed Tamara N.,AL-Mayah Saif Jabbar Yasir
The urgent need for precise quantification of a crucial prognostic tumor marker, a human epidermal growth factor receptor 2 (HER2), is of paramount importance for health institutions in screening, diagnosis, and the therapeutic trip of breast cancer. A conspicuous analysis of the extracellular domain of the human epidermal growth factor receptor 2 (HER2-ECD) was conducted using a sandwich electrochemical immunosensing assay on nanomaterial-modified screen-printed carbon electrode (SPCE) surfaces. The SPCEs modified with carboxylated multiwalled carbon nanotubes combined with Fe/Cu bimetallic 1,4-benzenedicarboxylic acid metal-organic frameworks loaded with AgNPs as a sensing platform for carrying capture antibody. The antibody-antigen interaction was identified utilizing horseradish peroxidase (HRP) conjugated detection antibody and 3,3’,5,5’-tetramethylbenzidine (TMB) as the enzymatic substrate. The structural, compositional, and morphological properties of synthesized nanomaterials were characterized by ( FT.IR, XRD, EDX, and FESEM ), before evaluating the analytical performance. The electrochemical signals were obtained by cyclic voltammetry, differential pulse voltammetry, and square wave voltammetry. Linear calibration plots were generated between 20 and 200 pg/mL, and limits of detection (LODs) were identified to be of 5.5 pg/mL, 5.65 pg/mL, and 3.96 pg/mL (for CV, DPV, and SWV), respectively, all much below the defined cut-off value of 15 ng/mL for this cancer biomarker. An immunosensor that had been designed expressly for the purpose of detecting the tumor marker in serum was utilized in order to conduct an experimental evaluation of the procedure’s effectiveness.
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DOI
高影响因子
Nanoscale Research Letters
·
2021
·Vol. 16
·期 1
·1-12
·
IF 4.703
Shu Mengjun,Gao Feng,Zeng Min,Yu Chulang,Wang Xue,Huang Renhua,Yang Jianhua,Su Yanjie,Hu Nantao,Zhou Zhihua,Liu Ke,Yang Zhi,Tan Hongtao,Xu Lin
To achieve better antitumour efficacy, it is urgent to improve anticancer drug delivery efficiency in targeting cancer cells. In this work, chitosan-functionalized graphene oxide (ChrGO) nanosheets were fabricated via microwave-assisted reduction, which were employed to the intracellular delivery nanosystem for anticancer drug agent in breast cancer cells. Drug loading and release research indicated that adriamycin can be efficiently loaded on and released from the ChrGO nanosheets. Less drug release during delivery and better biocompatibility of ChrGO/adriamycin significantly improve its safety and therapeutic efficacy in HER2-overexpressing BT-474 cells. Furthermore, ChrGO/adriamycin in combination with trastuzumab exhibited synergistic antitumour activity in BT-474 cells, which demonstrated superior therapeutic efficacy compared with each drug alone. Cells treated with trastuzumab (5 μg/mL) or equivalent ChrGO/adriamycin (5 μg/mL) each elicited 54.5% and 59.5% cell death, respectively, while the combination treatment with trastuzumab and ChrGO/adriamycin resulted in a dramatic 88.5% cell death. The dual-targeted therapy displayed higher apoptosis, indicating superior therapeutic efficacy due to the presence of different mechanisms of action. The combined treatment of ChrGO/adriamycin and trastuzumab in BT-474 cells induced cell cycle arrest and apoptosis, which ultimately led to the death of augmented cancer cells. This work has provided a facile microwave-assisted fabrication of ChrGO as a controlled and targeted intracellular drug delivery nanosystem, which is expected to be a novel promising therapy for treating HER2-overexpressing breast cancer cells.
研究领域:
癌症研究
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纳米医学
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药物递送系统
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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
ANALYST
·
2021
·Vol. 146
·期 22
·6893-6901
·
IF 4.616
Hui Chen,Longqiang Xing,Huiru Guo,Caixia Luo,Xuedian Zhang
A graphene oxide (GO)-based nanocarrier that imparts tumor-selective delivery of dual-drug with enhanced therapeutic index, is introduced. GO is conjugated with Au@Ag and Fe3O4 nanoparticles, which facilitates it with SERS tracking and magnetic targeting abilities, followed by the covalent binding of the anti-HER2 antibody, thus allowing it to both actively and passively target SKBR3 cells, human breast cancer cells expressed with HER2. Intracellular drug delivery behaviors are probed using SERS spectroscopy in a spatiotemporal manner, which demonstrates that nanocarriers are internalized into the lysosomes and release the drug in response to the acidic microenvironment. The nanocarriers loaded with dual-drug possess increased cancer cytotoxicity in comparison to those loaded with a single drug. Attractively, the enhanced cytotoxicity against cancer cells is achieved with relatively low concentrations of the drug, which is demonstrated to be involved in the drug adsorption status. These results may give us the new prospects to design GO-based delivery systems with rational drug dosages, thus achieving optimal therapeutic response of the multi-drug with increased tumor selectivity and reduced side effects.
研究领域:
纳米技术
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药学
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生物医学工程
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癌症研究
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2023
·
IF 8.9
Jie Wang,Robert Dallmann,Renquan Lu,Jing Yan,Jérôme Charmet
Immunoaffinity-based liquid biopsies of circulating tumor cells (CTCs) hold great promise for cancer management but typically suffer from low throughput, relative complexity, and postprocessing limitations. Here, we address these issues simultaneously by decoupling and independently optimizing the nano-, micro-, and macro-scales of an enrichment device that is simple to fabricate and operate. Unlike other affinity-based devices, our scalable mesh approach enables optimum capture conditions at any flow rate, as demonstrated with constant capture efficiencies, above 75% between 50 and 200 μL min–1. The device achieved 96% sensitivity and 100% specificity when used to detect CTCs in the blood of 79 cancer patients and 20 healthy controls. We demonstrate its postprocessing capacity with the identification of potential responders to immune checkpoint inhibition (ICI) therapy and the detection of HER2 positive breast cancer. The results compare well with other assays, including clinical standards. This suggests that our approach, which overcomes major limitations associated with affinity-based liquid biopsies, could help improve cancer management.
研究领域:
肿瘤学
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生物医学工程
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分子生物学
·
临床诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Pharmaceutics-X
·
2024
·
IF 5.2
Xing Liu,Wenwen Shen
In this study, the trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib (Tra-CM-MSN-PYR) were prepared for targeted therapy of HER2-positive breast cancer. Transmission electron microscopy (TEM) characterization showed that MSN had a spherical morphology with mesoporous channels and that the structure of Tra-CM-MSN was a cell membrane (CM) layer successfully coated on the surface of MSN. A cellular uptake assay demonstrated that FITC-labeled Tra-CM-MSN were taken up by SK-BR-3 breast cancer cells, which illustrated that Tra-CM-MSN had good targeting ability compared with CM-MSN and MSN. In vivo imaging experiments demonstrated significant accumulation of FITC-labeled Tra-CM-MSN in tumor tissues, further proving that Tra-CM-MSN have superior targeting properties. Cell apoptosis experiments suggested that Tra-CM-MSN-PYR significantly inhibited the proliferation of SK-BR-3 breast cancer cells. The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2023
·Vol. 190
·期 10
·1-8
·
IF 5.7
Qiu Minghao,Ren Yuqing,Huang Lumin,Zhu Xueying,Liang Tikai,Li Meijin,Tang Dianping
The proof-of-concept of sensitive electrochemical immunoassay for the quantitative monitoring of human epidermal growth factor receptor 2 (HER2) is reported. The assay is carried out on iron nitrogen-doped carbon (FeNC) nanozyme-modified screen-printed carbon electrode using chronoamperometry. Introduction of target HER2 can induce the sandwiched immunoreaction between anti-HER2 monoclonal antibody-coated microplate and biotinylated anti-HER2 polyclonal antibody. Thereafter, streptavidin-glucose oxidase (GOx) conjugate is bonded to the detection antibody. Upon addition of glucose, 3,3′,5,5′-tetramethylbenzidine (TMB) is oxidized through the produced H 2 O 2 with the assistance of GOx and FeNC nanozyme. The oxidized TMB is determined via chronoamperometry. Experimental results revealed that electrochemical immunosensing system exhibited good amperometric response, and allowed the detection of target HER2 as low as 4.5 pg/mL. High specificity and long-term stability are acquired with FeNC nanozyme-based sensing strategy. Importantly, our system provides a new opportunity for protein diagnostics. Graphical Abstract
研究领域:
生物医学工程
·
分析化学
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纳米技术
·
癌症诊断
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Xiaoxi Guo,Shuping Liu,Minghui Yang,Huitong Du,Fengli Qu
Photoelectrochemical (PEC) biosensor for highly sensitive detection of breast cancer biomarker human epidermal growth factor receptor-2 (HER2) is reported utilizing a dual signal amplification strategy. The biosensor was prepared based on tungsten sulfide nanowire array on Ti mesh (WS 2 NW/TM). Such WS 2 NW/TM electrode can generate photoelectric signal under visible light excitation . The HER2 aptamer was wrapped onto the nanowire array surface for specific binding with HER2 molecules, and gold nanoparticles (Au NPs) that modified with glucose oxidase (GOx) and HER2 binding peptide was utilized for signal amplification. The H 2 O 2 that generated by GOx catalyzed glucose reaction and localized surface plasmon resonance of Au NPs can both enhance the PEC current intensity of the biosensor, leading to dual signal amplification. The PEC current intensity is enhanced linearly with HER2 concentration in the 0.5–10 ng/mL range with limit of detection of 0.36 ng/mL. Such biosensor was applied for the detection of HER2 in breast cancer serum samples with detection results in good agreement with commercial ELISA results.
研究领域:
生物医学工程
·
纳米技术
·
癌症生物学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）