DRUG DELIVERY
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2018
·
IF 3.095
Yiwen You,Zhiyuan Xu,Yun Chen
HER2-positive breast cancer correlates with more aggressive tumor growth, a poorer prognosis and reduced overall survival. Currently, trastuzumab (Herceptin), which is an anti-HER2 antibody, is one of the key drugs. There is evidence indicating that conjugation of trastuzumab with chemotherapy drugs, such as doxorubicin (DOX), for multiple targets could be more effective. However, incomplete penetration into tumors has been noted for those conjugates. Compared to an antibody, peptides may represent an attractive alternative. For HER2, a similar potency has been observed for a 12-amino-acid anti-HER2 peptide mimetic YCDGFYACYMDV-NH2 (AHNP, disulfide-bridged) and full-length trastuzumab. Thus, a peptide, GPLGLAGDDYCDGFYACYMDV-NH2, which consists of AHNP and an MMP-2 cleavable linker GPLGLAGDD, was first designed, followed by conjugation with DOX via a glycine residue at the N-terminus to form a novel DOX-peptide conjugate MAHNP-DOX. Using HER2-positive human breast cancer cells BT474 and SKBR3 as in vitro model systems and nude mice with BT474 xenografts as an in vivo model, this conjugate was comprehensively characterized, and its efficacy was evaluated and compared with that of free DOX. As a result, MAHNP-DOX demonstrated a much lower in vitro IC50, and its in vivo extent of inhibition in mice was more evident. During this process, enzymatic cleavage of MAHNP-DOX is critical for its activation and cellular uptake. In addition, a synergistic response was observed after the combination of DOX and AHNP. This effect was probably due to the involvement of AHNP in the PI3K–AKT signaling pathway, which can be largely activated by DOX and leads to anti-apoptotic signals.
研究领域:
肿瘤学
·
药学
·
分子生物学
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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
IEEE TRANSACTIONS ON NANOBIOSCIENCE
·
2022
·Vol. 22
·期 3
·655-663
·
IF 3.206
Shenfei Zong,Cheng Cao,Kejian Chen,Yiping Cui,Jia Li,Zhuyuan Wang
In recent years, nanoparticles camouflaged by red blood cell membrane (RBCM) have become a potential nano-drug delivery platform due to their good biocompatibility and immune evasion capability. Here, a multifunctional drug nanocarrier based on RBCM camouflaged mesoporous silica nanorods (MSNR) is presented, which can be used in pH and near-infrared (NIR) light triggered synergistic chemo-photothermal killing of cancer cells. To fabricate such a nanocarrier, MSNR and RBCM were prepared by the sol-gel method and modified hypotonic lysis method, respectively. Drugs were loaded into the pores of MSNR. Finally, RBCM was coated on the surface of MSNR by extrusion through a polycarbonate membrane. The advantages of the nanocarrier include: 1) MSNR can induce more cellular uptake than sphere shaped mesoporous silica nanoparticles. 2) The RBCM can reduce drug leakage and prevent clearance of the nanocarriers by macrophages. 3) By simultaneous loading doxorubicin (DOX) and indocyanine green (ICG), pH and NIR triggered synergistic chemo-photothermal therapy can be realized. In the experiment, we studied the drug releasing and cellular uptake of the nanocarriers in a breast cancer cell line (SKBR3 cells), in which a sufficient killing effect was observed. Such a multifunctional drug nanocarrier holds a broad application prospect in cancer treatment.
研究领域:
纳米技术
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癌症研究
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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
JOURNAL OF NANOPARTICLE RESEARCH
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2013
·Vol. 15
·期 10
·1-10
·
IF 2.175
Li Jia,An Yan-Li,Zang Feng-Chao,Zong Shen-Fei,Cui Yi-Ping,Teng Gao-Jun
We report a composite nanoprobe based on silica-coated magnetic nanoparticles (NPs) for distinguishing breast cancers at different HER2 statuses. The nanoprobe has a core–shell structure, with Fe 3 O 4 NPs as the magnetic core and dye-embedded silica as the fluorescent shell, whose average size is about 150 nm. Besides, the outmost surfaces of the probes were modified with specific antibodies to endow the probe with a targeting ability. With such a structure, the nanoprobe can accomplish dual mode targeting of human breast cancer cells based on fluorescence and magnetic resonance imaging (MRI). In the experiments, three human breast cancer cell lines were used to test the targeting ability of the nanoprobe. Specifically, SKBR3 cells with a high HER2 expression level were used as the model target cells, while MCF7 cells with a lower HER2 expression levels and HER2-negative MDA-MB-231 cells were used as the controls. Both the fluorescence and MRI imaging results confirmed that the nanoprobe can distinguish three cancer cell lines with different HER2 expression levels. With the dual mode imaging and specific targeting properties, we anticipate that the presented nanoprobe may have a great potential in the diagnosis and treatment of cancerous diseases.
研究领域:
癌症研究
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纳米技术
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医学成像
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生物医学工程
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产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Wang Wenrui,Zhou Mengyang,Xu Yang,Peng Wei,Zhang Shiwen,Li Rongjie,Zhang Han,Zhang Hui,Cheng Shumin,Wang Youjing,Wei Xinyu,Yue Chengxu,Yang Qingling,Chen Changjie
Multidrug resistance (MDR) is a serious problem during cancer therapy. The purpose of the present study was to formulate D-α-Tocopheryl polyethylene glycol 1000 succinate-resveratrol-solid lipid nanoparticles (TPGS-Res-SLNs) to improve its therapeutic efficacy against breast cancer. In this study, the solvent injection method was used to prepare the TPGS-Res-SLNs. It was found that the TPGS-Res-SLNs exhibited zeta potential and drug-loading of −25.6 ± 1.3 mV and 32.4 ± 2.6%, respectively. Therefore, it was evident that the TPGS-Res-SLNs can increase cellular uptake of chemotherapeutic drugs, induce mitochondrial dysfunction, and augment tumor treatment efficiency by inducing apoptosis. Moreover, it was found that SKBR3/PR cells treated with TPGS-Res-SLNs exhibited significant inhibition of cell migration and invasion, as compared with free resveratrol. In addition, results from in vivo SKBR3/PR xenograft tumor models revealed that TPGS-Res-SLNs has better efficacy in promoting apoptosis of tumor cells owing to high therapeutic outcomes on tumors when compared with the efficacy of free resveratrol. In conclusion, the findings of the present study indicate significant potential for use of TPGS-Res-SLNs as an efficient drug delivery vehicle to overcome drug resistance in breast cancer therapy.
研究领域:
药学
·
肿瘤学
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纳米技术
·
药物递送系统
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癌症治疗
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Tianbao Dong,Chaowei Han,Xin Liu,Zhichao Wang,Yanhui Wang,Qing Kang,Pengcheng Wang,Feimeng Zhou
Cell-based kinetic studies of ligand or candidate drug binding to membrane proteins have produced affinity and kinetic values that are different from measurements using purified proteins. However, ligand binding to fixated cells whose membrane constituents (e.g., proteins and their glycosylated forms) are partially connected by a cross-linking reagent has not been compared to that to live cells. Under the same experimental conditions for the LigandTracer method, we measured the interactions of fluorophore-labeled lectins and antibody molecules with glycans at HFF cells and the human epithelial growth receptor 2 at SKBR3 cells, respectively. In conjunction with surface plasmon resonance microscopy, the effects of labels and cell/sub-cell heterogeneity on binding kinetics were investigated. Our results revealed that, for cell constituents whose structures and functions are not closely dependent on cell viability, the ligand binding kinetics at fixated cells is only slightly different from that at live cells. The altered kinetics is explained on the basis of a less mobile receptor confined in a local environment created by partially interconnected protein molecules. We show that cell/sub-cell heterogeneity and labels on the ligands can alter the binding reaction more significantly. Thus, fixating cells not only simplifies experimental procedures for drug screening and renders assays more robust but also provides reliable kinetic information about drug binding to cell constituents whose structures are not changed by chemical fixation.
研究领域:
生物物理学
·
细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）