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纳米金刚石的分散、修饰及载药应用研究

秦世荣 赵琪 程振国 苏丽霞 单崇新

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纳米金刚石的分散、修饰及载药应用研究

秦世荣, 赵琪, 程振国, 苏丽霞, 单崇新

Disintegration, functionalization and drug-delivery application of nanodiamond

Qin Shi-Rong, Zhao Qi, Cheng Zhen-Guo, Su Li-Xia, Shan Chong-Xin
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  • 纳米金刚石(nanodiamond,ND)作为一种重要的碳纳米材料,具有表面易修饰、比表面积大、生物毒性低以及物理化学稳定性好等特点,使其在生物医学领域具有独特的优势.本文通过对ND进行分散和化学修饰得到了分散性良好的羧基化纳米金刚石(ND-COOH),并通过透射电子显微镜、X-射线衍射、傅里叶变换红外谱仪等手段对其形貌和结构进行了表征分析.ND-COOH在水溶液中水解后呈现出较高的负电位,致使其可以通过静电相互作用吸附带正电的抗癌药物盐酸阿霉素(dox),且对阿霉素的负载量可达325 μg/mg.由于ND-COOH与dox之间通过带负电的羧酸根与带正电的质子化氨基结合,因此在H+浓度较高的酸性溶液中,药物复合体ND-dox呈现出显著的pH值依赖药物释放特性,在pH值为5.0的磷酸盐缓冲液中药物释放率达到85%,而在pH值为7.4的PBS中药物释放率低于40%.此外,ND-COOH和ND-dox的细胞毒性和体外细胞杀伤能力结果表明,ND-COOH在0–150 μg/mL范围内对细胞活性没有明显抑制,而ND装载药物dox后的ND-dox对SGC-7901胃癌细胞活性则表现出显著的抑制作用,表明ND-COOH作为药物载体具有较低的生物毒性,而负载药物后则对肿瘤细胞具有较强的杀伤能力.通过对ND进行简单的分散和表面改性,使ND具备良好的药物装载和独特的pH值依赖药物释放特性,这对于促进纳米金刚石在药物载体方面的应用具有重要的借鉴意义.
    In recent years, with the rapid development of nanomedicine, the nanomaterials for bio-medical applications have received much attention. Although there are a variety of nanomaterials such as lipid, carbon nanotube, etc. that have been studied as drug carrier, they are restricted by the potential toxicity and high cost of production. So, it is necessary to find a good alternative for the future drug delivery applications. Detonation nanodiamond, as an important carbon nanomaterial, possesses many excellent properties such as facile functionalization, large specific surface area, low toxicity and high chemical stability and so on, which make them advantageous in bio-medical applications over many other nanomaterials. In this work, the carboxyl functionalized and well-dispersed nanodiamond (ND-COOH) is obtained through disintegration and chemical modification, and then the functionalized nanodiamond is characterized by transmission electron microscope, X-ray diffraction, Fourier transform infrared spectroscopy, etc. to analyze its morphology and structure and the toxicity. Besides, the drug loading and release properties are also examined. The ND-COOH exhibits high zeta potential in aqueous solution, which enables them adsorb doxorubicin (dox) molecules onto the surface through electrostatic interaction, and the maximal loading reaches to 325 μg/mg, which is higher than most of reported results. It is because the bond between dox and ND-COOH origins from the electrostatic attraction between negatively charged-COO- on the ND and positively charged–NH3 in the dox. So, when the drug compounds are dispersed into low pH environment, the high H+ concentration would promote the transformation of –COO- into –COOH, which would weaken the electrostatic attraction between ND and dox and hence accelerate the drug release. This leads a drug release to reach 85% in pH 5.0 PBS and less than 40% in pH 7.4 PBS, exhibiting interesting pH-responsive drug release behavior. Finally, the toxicity and in vitro cancer cell killing results of ND-COOH and ND-dox preliminarily show that in the concentration range from 0 to 150 μg/mL, the functionalized ND-COOH does not inhibit the viability of SGC-7901 cells, exhibiting low toxicity. In contrast, the ND-dox shows obvious cytotoxicity towards SGC-7901 cells by strongly inhibiting their viability to lower than 40% in 150 μg/mL group. This work details and systematically discusses the disintegration, functionalization, drug loading and release properties of ND, which would be significant in promoting the biomedical application of ND.
      通信作者: 赵琪, zhaoqiv@126.com;cxshan@zzu.edu.cn ; 单崇新, zhaoqiv@126.com;cxshan@zzu.edu.cn
    • 基金项目: 国家自然科学基金青年科学基金(批准号:21601159)和国家自然科学基金杰出青年科学基金(批准号:61425021)资助的课题.
      Corresponding author: Zhao Qi, zhaoqiv@126.com;cxshan@zzu.edu.cn ; Shan Chong-Xin, zhaoqiv@126.com;cxshan@zzu.edu.cn
    • Funds: Project supported by the Young Scientists Fund of the National Natural Science Foundation of China (Grant No. 21601159) and the National Science Fund for Distinguished Young Scholars of China (Grant No. 61425021).
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    Turcheniuk K, Trecazzi C, Deeleepojananan C, Mochalin V N 2016 ACS Appl. Mater. Interfaces 8 25461

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    Dong Y, Cao R, Li Y, Wang Z, Li L, Tian L 2015 RSC Adv. 5 82711

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  • [1]

    Etheridge M L, Campbell S A, Erdman A G, Haynes C L, Wolf S M, Mccullough J 2013 Nanomed. Nanotechnol. 9 1

    [2]

    Wang P W, Liu M J, Jiang L 2016 Acta Phys. Sin. 65 56 (in Chinese) [王鹏伟, 刘明杰, 江雷 2016 物理学报 65 56]

    [3]

    Byrne J D, Betancourt T, Brannon-Peppas L 2008 Adv. Drug Deliver. Rev. 60 1615

    [4]

    Shi J, Wang L, Zhang J, Ma R, Gao J, Liu Y, Zhang C, Zhang Z 2014 Biomaterials 35 5847

    [5]

    Michalet X, Pinaud F F, Bentolila L A, Tsay J M, Doose S, Li J, Sundaresan G, Wu A, Gambhir S S, Weiss S 2005 Science 307 538

    [6]

    Taton T A, Mirkin C A, Letsinger R L 2000 Science 289 1757

    [7]

    Wang X H, Zhou Y H 2009 Acta Phys. Sin. 58 4239 (in Chinese) [王兴和, 周延怀 2009 物理学报 58 4239]

    [8]

    Xiong P, Guo P, Xing D, He J S 2006 Acta Phys. Sin. 55 4383 (in Chinese) [熊平, 郭萍, 向东, 何继善 2006 物理学报 55 4383]

    [9]

    Ju H, Roy R A, Murray T W 2013 Biomed. Opt. Express 4 66

    [10]

    Xu C, He W, L Y, Qin C, Shen L, Yin L 2015 Int. J. Pharm. (Amsterdam, Neth.) 493 172

    [11]

    Cho K, Wang X, Nie S, Chen Z, Shin D 2008 Clin. Cancer Res. 14 1310

    [12]

    Slowing I I, Trewyn B G, Giri S, Lin V S Y 2010 Adv. Funct. Mater. 17 1225

    [13]

    Sinha R, Kim G J, Nie S, Shin D M 2006 Mol. Cancer Ther. 5 1909

    [14]

    Labhasetwar V, Song C, Levy R J 1997 Adv. Drug Deliver. Rev. 24 63

    [15]

    Yu S, Kang M, Chang H, Chen K, Yu Y C2006 J. Am. Chem. Soc. 127 17604

    [16]

    Vaijayanthimala V, Tzeng Y, Chang H, Li C 2009 Nanotechnology 20 425103

    [17]

    Vaijayanthimala V, Cheng P, Yeh S, Liu K, Hsiao C, Chao J, Chang H 2012 Biomaterials 33 7794

    [18]

    Dahl J E, Liu S, Carlson R M K 2003 Science 299 96

    [19]

    Arnault J C 2015 Novel Aspects of Diamond 121 85

    [20]

    Zhang Q, Mochalin V N, Neitzel I, Knoke I Y, Han J, Klug C A, Zhou J, Lelkes P I, Gogotsi Y 2011 Biomaterials 32 87

    [21]

    Liu Y, Gu Z, Margrave J L, Khabashesku V N 2004 Chem. Mater. 16 3924

    [22]

    Zhang X, Chen M, Lam R, Xu X, Osawa E, Ho D 2009 ACS Nano 3 2609

    [23]

    Krueger A, Ozawa M, Jarre G, Liang Y, Stegk J, Lu L 2007 Phys. Status Solidi A 204 2881

    [24]

    Krger A, Kataoka F, Ozawa M, Fujino T, Suzuki Y, Aleksenskii A E, Vul A Y, Ōsawa E 2005 Carbon 43 1722

    [25]

    Turcheniuk K, Trecazzi C, Deeleepojananan C, Mochalin V N 2016 ACS Appl. Mater. Interfaces 8 25461

    [26]

    Aleksenskiy A E, Eydelman E D, Vul A Y 2011 Nanosci. Nanotechnol. Lett. 3 68

    [27]

    Dong Y, Cao R, Li Y, Wang Z, Li L, Tian L 2015 RSC Adv. 5 82711

    [28]

    Yan J, Guo Y, Altawashi A, Moosa B, Lecommandoux S, Khashab N M 2012 New J. Chem. 36 1479

    [29]

    Das G, Nicastri A, Coluccio M L, Gentile F, Candeloro P, Cojoc G, Liberale C, Angelis F D, Fabrizio E D 2010 Microsc. Res. Tech. 73 991

    [30]

    Dong H, Sun X J, Zhang X, Yang D D, Wang X L, Zhang F M 2018 Mater. Rev. 2 189 (in Chinese) [董鸿, 孙晓君, 张欣, 杨豆豆, 王雪亮, 张凤鸣 2018 材料导报 2 189]

    [31]

    Sun C, Qin C, Wang X, Yang G, Shao K, Lan Y, Su Z, Huang P, Wang C, Wang E 2012 Dalton Trans. 41 6906

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出版历程
  • 收稿日期:  2018-05-01
  • 修回日期:  2018-05-17
  • 刊出日期:  2019-08-20

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