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Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for targeted delivery of doxorubicin

机译:含叶酸的还原敏感性脂质-聚合物杂化纳米颗粒,用于阿霉素的靶向递送

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The development and evaluation of folate-targeted and reduction-triggered biodegradable nanoparticles are introduced to the research on targeted delivery of doxorubicin (DOX). This type of folate-targeted lipid-polymer hybrid nanoparticles (FLPNPs) is comprised of a poly(D,L-lactide-co-glycolide) (PLGA) core, a soybean lecithin monolayer, a monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C-16) reduction-sensitive shell, and a folic acid-targeted ligand. FLPNPs exhibited high size stability but fast disassembly in a simulated cancer cell reductive environment. The experiments on the release process in vitro revealed that as a reduction-sensitive drug delivery system, FLPNPs released DOX faster in the presence of 10 mM dithiothreitol (DTT). Results from flow cytometry, confocal image and in vitro cytotoxicity assays revealed that FLPNPs further enhanced cell uptake and generated higher cytotoxicity against human epidermoid carcinoma in the oral cavity than non-targeted redox-sensitive and targeted redox-insensitive controls. Furthermore, in vivo animal experiments demonstrated that systemic administration of DOX-loaded FLPNPs remarkably reduced tumor growth. Experiments on biodistribution of DOX-loaded FLPNPs showed that an increasing amount of DOX accumulated in the tumor. Therefore, FLPNPs formulations have proved to be a stable, controllable and targeted anticancer drug delivery system.
机译:以叶酸为靶标和还原触发的可生物降解纳米颗粒的开发和评估被引入到阿霉素靶向输送的研究中。这种以叶酸为靶标的脂质-聚合物杂化纳米颗粒(FLPNPs)由聚(D,L-丙交酯-乙交酯)(PLGA)核,大豆卵磷脂单层,单甲氧基-聚(乙二醇)-SS组成-十六烷基(mPEG-SSC-16)还原敏感的外壳,以及叶酸靶向的配体。 FLPNPs在模拟的癌细胞还原环境中显示出高尺寸稳定性,但分解速度很快。体外释放过程的实验表明,作为一种对还原敏感的药物输送系统,FLPNP在10 mM二硫苏糖醇(DTT)的存在下能更快地释放DOX。流式细胞术,共聚焦图像和体外细胞毒性试验的结果表明,与非靶向氧化还原敏感和靶向氧化还原不敏感的对照相比,FLPNPs进一步增强了细胞摄取,并在口腔中产生了针对人表皮癌的更高细胞毒性。此外,体内动物实验表明,全身性给药装载DOX的FLPNPs显着降低了肿瘤的生长。载有DOX的FLPNPs的生物分布实验表明,在肿瘤中积累了越来越多的DOX。因此,已证明FLPNPs制剂是稳定,可控和靶向的抗癌药物递送系统。

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