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Pluronic F127-chondroitin sulfate micelles prepared through a facile method for passive and active tumor targeting

机译：Pluronic F127-软骨素通过用于被动和活性肿瘤靶向的容易方法制备的硫酸盐胶束制备

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摘要

Tumor-specific drug delivery is still a challenge in cancer therapy. Passive tumor targeting strategies, such as the enhanced permeability and retention (EPR) effect, cause nanocarriers to accumulate in tumors. However, this strategy can not provide specific tumor targeting. In this study, Pluronic F127 (PF127), a block copolymer which can inhibit drug efflux transporters in cancer therapy, was modified to form tumor-specific micelles with a natural polysaccharide, chondroitin sulfate (ChS), which imparts the site-specific property. A facile and efficient method based on Schiff base reaction was developed to facilitate both basic and clinical research. A series of PF127-ChS micelles with different ratios of PF127 and ChS were fabricated and evaluated in terms of size, morphology, drug loading efficiency and drug release behavior. Spherical micelles with a mean diameter of 155-241 nm were obtained. Their critical micelle concentration (CMC) was significantly reduced in contrast to PF127 micelles and their stability was enhanced. Doxorubicin (DOX) was loaded into the hydrophobic core of PF127 or adsorbed by ChS through electrostatic interactions with the negative charges of chondroitin sulfate. In vitro DOX release studies showed that DOX release from the micelles was enhanced at acidic pH values compared to physiological pH. A cytotoxicity assay (MTT) determined that the micelles possess significantly lower toxicity. Confocal microscopy and flow cytometry analysis indicated that DOX loaded micelles could efficiently release DOX inside cells by specific cellular uptake. These outcomes revealed that PF127-ChS micelles could be exploited as carriers for anti-tumor drugs for site-specific therapy of solid tumors.
机译：肿瘤特异性药物递送仍然是癌症治疗的挑战。被动肿瘤靶向策略，如在肿瘤的增强的渗透性和保留（EPR）效果，原因纳米载体积聚。然而，这种策略不能提供特定的肿瘤靶向。在该研究中，修饰Pluronic F127（PF127），可以抑制癌症治疗中药物流出转运蛋白的嵌段共聚物，以形成具有天然多糖的肿瘤特异性胶束，硫酸软骨素（CHS），其赋予现场特异性的性质。开发了一种基于Schiff基础反应的容易和有效的方法，促进基础和临床研究。在大小，形态，药物负载效率和药物释放行为方面制造和评估具有PF127和CHS不同比例的PF127-CHS胶束。获得平均直径为155-241nm的球形胶束。与PF127胶束相比，它们的临界胶束浓度（CMC）显着降低，并且它们的稳定性得到了增强。将多柔比星（DOX）加载到PF127的疏水芯中，或者通过与硫酸软骨素负荷的静电相互作用进行CHS吸附。体外Dox释放研究表明，与生理pH值相比，在酸性pH值下，从胶束上释放来自胶束的DOX释放。细胞毒性测定（MTT）确定胶束具有显着较低的毒性。共聚焦显微镜和流式细胞术分析表明，DOX装载的胶束可以通过特定的蜂窝摄取有效地释放细胞内部。这些结果显示，PF127-CHS胶束可以被利用为用于抗肿瘤药物的载体，用于实体瘤的特异性肿瘤的特异性治疗。

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  • 来源
    《RSC Advances》 |2016年第54期|共9页
  • 作者

    Lu Shaoyu; Gao Nannan; Cao Zhen; Gao Chunmei; Xu Xiubin; Bai Xiao; Feng Chen; Liu Mingzhu;

  • 作者单位

    Lanzhou Univ State Key Lab Appl Organ Chem Key Lab Nonferrous Met Chem &

    Resources Utilizat Lanzhou 730000 Peoples R China;

    Lanzhou Univ State Key Lab Appl Organ Chem Key Lab Nonferrous Met Chem &

    Resources Utilizat Lanzhou 730000 Peoples R China;

    Lanzhou Univ Sch Stomatol Lanzhou 730000 Peoples R China;

    Lanzhou Univ State Key Lab Appl Organ Chem Key Lab Nonferrous Met Chem &

    Resources Utilizat Lanzhou 730000 Peoples R China;

    Lanzhou Univ State Key Lab Appl Organ Chem Key Lab Nonferrous Met Chem &

    Resources Utilizat Lanzhou 730000 Peoples R China;

    Lanzhou Univ State Key Lab Appl Organ Chem Key Lab Nonferrous Met Chem &

    Resources Utilizat Lanzhou 730000 Peoples R China;

    Lanzhou Univ State Key Lab Appl Organ Chem Key Lab Nonferrous Met Chem &

    Resources Utilizat Lanzhou 730000 Peoples R China;

    Lanzhou Univ State Key Lab Appl Organ Chem Key Lab Nonferrous Met Chem &

    Resources Utilizat Lanzhou 730000 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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