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A green and facile method for the preparation of a pH-responsive alginate nanogel for subcellular delivery of doxorubicin

机译：用于制备亚霉素亚细胞递送pH响应藻酸盐纳米凝胶的绿色和容纳方法

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摘要

A surfactant-free and organic solvent-free one-pot method was utilized for the preparation of a pH-responsive alginate nanogel (pH-AN). Simply by mixing anionic sodium alginate (SA) with cationic doxorubicin (DOX) through electrostatic interactions, followed by in situ crosslinking with ionic calcium under ultrasound, a DOX-loaded pH-AN was obtained. The sizes of the nanogels can be tailored by varying the concentration of SA, the ratio of SA to ionic calcium and DOX. The nanogel was measured with a size range of 210 nm, and a polydispersity index of 0.208, as confirmed by transmission electron microscopy and dynamic light scattering. In vitro release profiles showed a significantly higher accumulative release at pH 5.0 than at pH 7.4, exhibiting apparent acid responsiveness. In vitro cytotoxicity tests clearly illustrated the remarkable inhibition to the growth of HeLa cells with an IC50 value of 0.26 mg mL(-1). In contrast, NIH 3T3 cells displayed high tolerance. The plain nanogel exclusive of DOX was practically non-toxic. Confocal laser scanning microscopy observation demonstrated that DOX was efficiently internalized into HeLa cells through endocytosis, released into the cytoplasm, and then principally entered the nuclei. It is clearly suggested that a green and facile method was proposed to achieve a pH-responsive nanogel carrier for the delivery of drugs.
机译：表面活性剂和无无有机溶剂的单釜法用于pH响应藻纳米凝胶​​（pH值-AN）的制备。简单地通过混合阴离子藻酸钠（SA）与多柔比星的阳离子（DOX）通过静电相互作用，随后在原位与下超声离子钙交联，得到DOX加载的pH值-AN。的纳米凝胶的尺寸可以通过改变SA，SA，以钙离子和DOX的比率的浓度来调整。纳米凝胶用的尺寸范围为210纳米，和0.208的多分散性指数测量，通过透射电子显微镜和动态光散射所证实。体外释放曲线显示在pH 5.0下一个显著更高累积释放比在pH 7.4下，表现出明显的酸响应性。在体外细胞毒性试验清楚地示出了显着的抑制HeLa细胞用0.26毫克毫升（-1）的IC 50值的增长。相比之下，NIH 3T3细胞表现出高耐受性。 DOX的普通絮状独家是几乎无毒。共聚焦激光扫描显微镜观察表明DOX被有效地通过内吞作用内在化到HeLa细胞，释放到细胞质中，然后进入主要的核。它明确提出，绿色和简便的方法，提出了以实现药品配送pH响应纳米凝胶的载体。

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  • 来源
    《RSC Advances》 |2015年第90期|共8页
  • 作者

    Xue Yanan; Xia Xiaoyang; Yu Bo; Luo Xiaogang; Cai Ning; Long Sihui; Yu Faquan;

  • 作者单位

    Wuhan Inst Technol Sch Chem Engn &

    Pharm Key Lab Green Chem Proc Minist Educ Hubei Key Lab Novel Reactor &

    Green Chem Technol Wuhan 430073 Hubei Peoples R China;

    Wuhan Inst Technol Sch Chem Engn &

    Pharm Key Lab Green Chem Proc Minist Educ Hubei Key Lab Novel Reactor &

    Green Chem Technol Wuhan 430073 Hubei Peoples R China;

    Wuhan Inst Technol Sch Chem Engn &

    Pharm Key Lab Green Chem Proc Minist Educ Hubei Key Lab Novel Reactor &

    Green Chem Technol Wuhan 430073 Hubei Peoples R China;

    Wuhan Inst Technol Sch Chem Engn &

    Pharm Key Lab Green Chem Proc Minist Educ Hubei Key Lab Novel Reactor &

    Green Chem Technol Wuhan 430073 Hubei Peoples R China;

    Wuhan Inst Technol Sch Chem Engn &

    Pharm Key Lab Green Chem Proc Minist Educ Hubei Key Lab Novel Reactor &

    Green Chem Technol Wuhan 430073 Hubei Peoples R China;

    Wuhan Inst Technol Sch Chem Engn &

    Pharm Key Lab Green Chem Proc Minist Educ Hubei Key Lab Novel Reactor &

    Green Chem Technol Wuhan 430073 Hubei Peoples R China;

    Wuhan Inst Technol Sch Chem Engn &

    Pharm Key Lab Green Chem Proc Minist Educ Hubei Key Lab Novel Reactor &

    Green Chem Technol Wuhan 430073 Hubei Peoples R China;

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