荔枝状CaCO3@HA/Fe3O4磁性介孔多级微球的制备

doi:10.15541/jim20180497

无机材料学报 ›› 2019, Vol. 34 ›› Issue (9): 925-932.DOI: 10.15541/jim20180497

所属专题：药物载体与防护材料

荔枝状CaCO₃@HA/Fe₃O₄磁性介孔多级微球的制备

肖文谦,张静,李克江,邹新宇,蔡昱东,李波(),刘雪(),廖晓玲

重庆科技学院纳微复合材料与器件重庆市重点实验室, 重庆 401331

收稿日期:2018-10-18 修回日期:2018-12-24 出版日期:2019-09-20 网络出版日期:2019-05-29
作者简介:肖文谦(1982-), 男, 博士, 讲师. E-mail: wqxiao@cqust.edu.cn
基金资助:
国家自然科学基金(11532004);国家自然科学基金(51603026);重庆市高校创新团队项目(CXTDX201601032);重庆市基础科学与前沿技术研究项目(CSTC2016jcyjA0541);重庆市基础科学与前沿技术研究项目(CSTC2018jcyjAX0711);重庆市基础科学与前沿技术研究项目(CSTC2015JCYJBX0003);重庆市教委科学技术研究项目(KJ1601301)

Litchi-like Superparamagnetic Hydroxyapatite Microspheres with Hierarchically Mesoporous Microspheres

XIAO Wen-Qian,ZHANG Jing,LI Ke-Jiang,ZOU Xin-Yu,CAI Yu-Dong,LI Bo(),LIU Xue(),LIAO Xiao-Ling

Chongqing Key Laboratory of Nano/Micro Composite Materials and Devices, Chongqing University of Science and Technology, Chongqing 401331, China

Received:2018-10-18 Revised:2018-12-24 Published:2019-09-20 Online:2019-05-29
Supported by:
National Natural Science Foundation of China(11532004);National Natural Science Foundation of China(51603026);Chongqing University Innovation Team Project(CXTDX201601032);Chongqing Research Program of Basic Research and Frontier Technology(CSTC2016jcyjA0541);Chongqing Research Program of Basic Research and Frontier Technology(CSTC2018jcyjAX0711);Chongqing Research Program of Basic Research and Frontier Technology(CSTC2015JCYJBX0003);Chongqing Municipal Education Commission Science and Technology Research Project(KJ1601301)

摘要/Abstract

摘要：

为了克服常规的生物陶瓷微球缺乏靶向功能的缺点, 本研究制备了内核为CaCO₃, 外壳为磁性可调控羟基磷灰石(HA)的新型荔枝状多孔微球。结果表明: 抗肿瘤药物阿霉素(DOX)能有效地负载于磁性HA微球上, 并具备磁性靶向功能。此外, HA外壳具有良好的生物相容性和pH响应特性, 可在模拟酸性肿瘤细胞环境中控制DOX的释放, 有效杀死肿瘤细胞, 并在模拟正常细胞培养环境中减少对正常细胞的毒副作用。这种新型的微球材料具有超顺磁性能, 且微结构可控, 是一种智能化药物控释微球载体, 可以灵敏地释放DOX, 从而有效地实现抗肿瘤活性。

关键词: 核壳结构, 微球, 羟基磷灰石, DOX

Abstract:

Due to the fact that the conventional bioceramic microspheres lack target function, novel litchi-like porous microspheres composed of a core of CaCO₃ and a tunable magnetic-hydroxyapatite (HA) shell were successfully prepared in this study. Antitumor drug, doxorubicin (DOX), was effectively loaded on the HA microspheres which possess magnetic targeting function. In addition, the HA shell, which had favorable biocompatibility and pH response characteristics, could be used to control release of loaded DOX from the litchi-like superparamagnetic microspheres in a simulated acidic tumor cell environment, effectively killing tumor cells and reducing toxic side effects to normal cells. The smart design presented in this study, which incorporates a tunable superparamagnetic shell and a controlled architecture, allows the sensitive release of drugs for efficient antitumor activity.

Key words: core-shell, microspheres, hydroxyapatite, DOX

中图分类号:

TQ174

肖文谦,张静,李克江,邹新宇,蔡昱东,李波,刘雪,廖晓玲. 荔枝状CaCO₃@HA/Fe₃O₄磁性介孔多级微球的制备[J]. 无机材料学报, 2019, 34(9): 925-932.

XIAO Wen-Qian,ZHANG Jing,LI Ke-Jiang,ZOU Xin-Yu,CAI Yu-Dong,LI Bo,LIU Xue,LIAO Xiao-Ling. Litchi-like Superparamagnetic Hydroxyapatite Microspheres with Hierarchically Mesoporous Microspheres[J]. Journal of Inorganic Materials, 2019, 34(9): 925-932.

图/表 10

图1 不同Fe3O4含量的超顺磁性CaCO3@HA/Fe3O4微球的SEM照片

Fig. 1 SEM images of superparamagnetic CaCO3@HA/Fe3O4 microspheres with different Fe3O4 component. Note: S0 (a1, a2), S1 (b1, b2), S2 (c1, c2), S3 (d1, d2)

图2 Fe3O4为25wt%的CaCO3@HA/Fe3O4微球水热转化前(a)后(b)的TEM照片

Fig. 2 TEM images before (a) and after (b) hydrothermal conversion of CaCO3@HA/Fe3O4 microspheres with 25wt% Fe3O4 component

图3 掺杂25wt% Fe3O4的CaCO3@HA/Fe3O4微球水热转化后的EDS图像

Fig. 3 Typical EDS patterns of HA microspheres with 25wt% Fe3O4 component

图4 不同Fe3O4含量荔枝状超顺磁性CaCO3@HA/Fe3O4微球的XRD图谱

Fig. 4 XRD patterns of CaCO3@HA/Fe3O4 microspheres with different Fe3O4 component

图5 不同Fe3O4掺杂含量的磁性CaCO3@HA/Fe3O4微球的等温吸附曲线(a)和孔径结构分布图(b)

Fig. 5 Typical nitrogen isothermal adsorption curves (a) and mesopore distribution (b) analysis of CaCO3@HA/Fe3O4 microspheres with different Fe3O4 content

图6 荔枝状超顺磁性CaCO3@HA/Fe3O4微球形成机理示意图

Fig. 6 Formation mechanism diagram of litchi-like superparamagnetic CaCO3@HA/Fe3O4 microspheres

图7 (a)荔枝状超顺磁性CaCO3@HA/Fe3O4微球悬浮液受磁铁吸引的数码照片, 及(b)300 K 下不同Fe3O4含量的CaCO3@HA/Fe3O4微球的磁滞回线

Fig. 7 Digital photographs (a) of the litchi-like CaCO3@HA/Fe3O4 magnetic HA microspheres in aqueous suspension and (b) magnetization of different samples as a function of the applied field measured at 300 K

表1 不同Fe3O4含量的CaCO3@HA/Fe3O4微球的比表面积(SBET)、载药量(DLA)和药物装载率(DLE)

Table 1 Fe3O4 content, specific surface area (SBET), drug loading amount (DLA) and drug loading efficiency (DLE) of CaCO3@HA/Fe3O4 microspheres

Sample	Fe₃O₄ content/wt%	S_BET/(m²·g^-1)	DLA /(mg·g^-1)	DLE/%
S1	16.08	196.481	96.88	96.88
S2	17.69	50.749	96.14	96.14
S3	37.98	46.623	97.96	97.96

图8 37 ℃下载药CaCO3@HA/Fe3O4微球在不同pH (3.4、5.7、7.4)的PBS中的DOX累计释放曲线

Fig. 8 DOX release profiles of the DOX-loaded litchi-like magnetic HA microspheres in PBS with different pH of 3.4, 5.7 and 7.3 at 37 ℃

图9 CCK8试验法测定正常细胞HaCaT(a)和肿瘤细胞HN6(b)在载DOX和不载DOX的CaCO3@HA/Fe3O4和CaCO3@HA微球下的24 h存活率柱状图

Fig. 9 CCK-8 assay of HaCaT (a) and HN6 tumor cells (b) co-cultured with unloaded or DOX-loaded litchi-like magnetic HA microspheres and litchi-like HA microspheres for 24 h

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荔枝状CaCO₃@HA/Fe₃O₄磁性介孔多级微球的制备

Litchi-like Superparamagnetic Hydroxyapatite Microspheres with Hierarchically Mesoporous Microspheres

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