一种具有谷胱甘肽/活性氧双响应和CD206靶向的紫杉醇前药纳米颗粒,以提高抗肿瘤效果

IF 3.8 4区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS IET nanobiotechnology Pub Date : 2023-04-13 DOI:10.1049/nbt2.12119
Changhai Wang, Yuwen Jiao, Xinyu Zhang, Mingxue Guo, Qing Zhang, Wenjun Hu, Shuang Dong, Tangthianchaichana Jakkree, Yang Lu, Jinling Wang
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引用次数: 0

摘要

紫杉醇作为一线抗癌药物,存在溶解度差、肿瘤细胞选择性不足等缺点,限制了其在临床中的进一步应用。因此,作者旨在利用前药和纳米技术的特点,制备一种活性氧(ROS)和谷胱甘肽双响应的靶向肿瘤前药纳米粒子Man-PEG-SS-PLGA/ProPTX,以改善紫杉醇局限性的临床应用现状。通过制备对Man-PEG-SS-PLGA/ProPTX进行了表征。采用细胞毒实验和流式细胞术研究纳米颗粒对肿瘤细胞的细胞毒作用及对肿瘤细胞凋亡的影响。通过检测肿瘤细胞的活性氧水平来研究纳米颗粒对活性氧的反应性。通过受体亲和实验和细胞摄取实验进一步研究了纳米颗粒对肿瘤细胞的选择性。Man-PEG-SS-PLGA/ProPTX的粒径为(132.90±1.81)nm,分散系数为0.13±0.03,Zeta电位为(−8.65±0.50)mV。包封率为95.46±2.31%,载药量为13.65±2.31%。纳米颗粒能显著抑制MCF-7、HepG2和MDA-MB-231肿瘤细胞的增殖和促进细胞凋亡。具有良好的ROS响应特性和靶向性。靶向摄取机制具有能量依赖性,内吞作用由非网格蛋白、非小窝蛋白、脂筏/小窝蛋白、环氧化酶(COX)/小窝蛋白介导,具有一定的浓度依赖性和时间依赖性。Man-PEG-SS-PLGA/ProPTX是一种对肿瘤微环境敏感的纳米颗粒,可以主动靶向肿瘤细胞。它限制了PTX在正常组织中的释放,增强了其对肿瘤细胞的选择性,具有显著的抗肿瘤活性,有望解决目前PTX使用的局限性。
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A paclitaxel prodrug nanoparticles with glutathion/reactive oxygen species dual-responsive and CD206 targeting to improve the anti-tumour effect

As a first-line anticancer drug, paclitaxel has shortcomings, such as poor solubility and lack of tumour cell selectivity, which limit its further applications in clinical practice. Therefore, the authors aimed to utilise the characteristics of prodrug and nanotechnology to prepare a reactive oxygen species (ROS) and GSH dual-responsive targeted tumour prodrug nanoparticle Man-PEG-SS-PLGA/ProPTX to improve the clinical application status of paclitaxel limitation. The characterisation of Man-PEG-SS-PLGA/ProPTX was carried out through preparation. The cytotoxicity of nanoparticles on tumour cells and the effect on apoptosis of tumour cells were investigated by cytotoxicity assay and flow cytometry analysis. The ROS responsiveness of nanoparticles was investigated by detecting the ROS level of tumour cells. The tumour cell selectivity of the nanoparticles was further investigated by receptor affinity assay and cell uptake assay. The particle size of Man-PEG-SS-PLGA/ProPTX was (132.90 ± 1.81) nm, the dispersion coefficient Polymer dispersity index was 0.13 ± 0.03, and the Zeta potential was (−8.65 ± 0.50) mV. The encapsulation rate was 95.46 ± 2.31% and the drug load was 13.65 ± 2.31%. The nanoparticles could significantly inhibit the proliferation and promote apoptosis of MCF-7, HepG2, and MDA-MB-231 tumour cells. It has good ROS response characteristics and targeting. The targeted uptake mechanism is energy-dependent and endocytosis is mediated by non-clathrin, non-caveolin, lipid raft/caveolin, and cyclooxygenase (COX)/caveolin with a certain concentration dependence and time dependence. Man-PEG-SS-PLGA/ProPTX is a tumour microenvironment-responsive nanoparticle that can actively target tumour cells. It restricts the release of PTX in normal tissues, enhances its selectivity to tumour cells, and has significant antitumour activity, which is expected to solve the current limitations of PTX use.

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来源期刊
IET nanobiotechnology
IET nanobiotechnology 工程技术-纳米科技
CiteScore
6.20
自引率
4.30%
发文量
34
审稿时长
1 months
期刊介绍: Electrical and electronic engineers have a long and illustrious history of contributing new theories and technologies to the biomedical sciences. This includes the cable theory for understanding the transmission of electrical signals in nerve axons and muscle fibres; dielectric techniques that advanced the understanding of cell membrane structures and membrane ion channels; electron and atomic force microscopy for investigating cells at the molecular level. Other engineering disciplines, along with contributions from the biological, chemical, materials and physical sciences, continue to provide groundbreaking contributions to this subject at the molecular and submolecular level. Our subject now extends from single molecule measurements using scanning probe techniques, through to interactions between cells and microstructures, micro- and nano-fluidics, and aspects of lab-on-chip technologies. The primary aim of IET Nanobiotechnology is to provide a vital resource for academic and industrial researchers operating in this exciting cross-disciplinary activity. We can only achieve this by publishing cutting edge research papers and expert review articles from the international engineering and scientific community. To attract such contributions we will exercise a commitment to our authors by ensuring that their manuscripts receive rapid constructive peer opinions and feedback across interdisciplinary boundaries. IET Nanobiotechnology covers all aspects of research and emerging technologies including, but not limited to: Fundamental theories and concepts applied to biomedical-related devices and methods at the micro- and nano-scale (including methods that employ electrokinetic, electrohydrodynamic, and optical trapping techniques) Micromachining and microfabrication tools and techniques applied to the top-down approach to nanobiotechnology Nanomachining and nanofabrication tools and techniques directed towards biomedical and biotechnological applications (e.g. applications of atomic force microscopy, scanning probe microscopy and related tools) Colloid chemistry applied to nanobiotechnology (e.g. cosmetics, suntan lotions, bio-active nanoparticles) Biosynthesis (also known as green synthesis) of nanoparticles; to be considered for publication, research papers in this area must be directed principally towards biomedical research and especially if they encompass in vivo models or proofs of concept. We welcome papers that are application-orientated or offer new concepts of substantial biomedical importance Techniques for probing cell physiology, cell adhesion sites and cell-cell communication Molecular self-assembly, including concepts of supramolecular chemistry, molecular recognition, and DNA nanotechnology Societal issues such as health and the environment Special issues. Call for papers: Smart Nanobiosensors for Next-generation Biomedical Applications - https://digital-library.theiet.org/files/IET_NBT_CFP_SNNBA.pdf Selected extended papers from the International conference of the 19th Asian BioCeramic Symposium - https://digital-library.theiet.org/files/IET_NBT_CFP_ABS.pdf
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