氢氧化铝纳米片: 结构依赖性癌症化疗药物的储运

doi:10.15541/jim20190052

无机材料学报 ›› 2020, Vol. 35 ›› Issue (2): 250-256.DOI: 10.15541/jim20190052

所属专题：生物材料论文精选(2020)；【虚拟专辑】药物递送(2020~2021)

• 研究快报 • 上一篇

氢氧化铝纳米片: 结构依赖性癌症化疗药物的储运

LI Xia¹,SHENASHEN Mohamed A¹,MEKAWY Moataz¹,TANIGUCHI Akiyoshi^2,³,EI-SAFTY Sherif A^1,³()

1. Research Center for Functional Materials, National Institute for Materials Science, Ibaraki 305-0047, Japan
2. Cellular Functional Nanomaterials Group, Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Ibaraki 305-0044, Japan
3. Engineering and Advanced Manufacturing, University of Sunderland, Sunderland, United Kingdom

收稿日期:2019-01-25 修回日期:2019-08-06 出版日期:2020-02-20 网络出版日期:2019-09-04
作者简介:李霞(1980-), 女, 博士. E-mail: lixia6969@hotmail.com

Aluminum Hydroxide Nanosheets with Structure-dependent Storage and Transportation toward Cancer Chemotherapy

LI Xia¹,SHENASHEN Mohamed A¹,MEKAWY Moataz¹,TANIGUCHI Akiyoshi^2,³,EI-SAFTY Sherif A^1,³()

1. Research Center for Functional Materials, National Institute for Materials Science, Ibaraki 305-0047, Japan
2. Cellular Functional Nanomaterials Group, Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Ibaraki 305-0044, Japan
3. Engineering and Advanced Manufacturing, University of Sunderland, Sunderland, United Kingdom

Received:2019-01-25 Revised:2019-08-06 Published:2020-02-20 Online:2019-09-04
Supported by:
National Institute for Materials Science of Japan

摘要/Abstract

摘要：

铝盐佐剂具有极好的安全记录, 是各种人类疫苗中唯一获得FDA许可的无机佐剂。据我们所知, 目前尚没有关于将其用作化疗药物的递送系统、并系统阐明其结构与载药性能之间关系的研究报道。本研究采用三嵌段共聚物、通过调节反应时间合成了具有可调比表面积和孔径的氢氧化铝(AlOOH)纳米片。AlOOH 纳米片的最大比表面积达470 m ²/g。其负载化疗药物阿霉素的能力与材料结构密切相关: 比表面积和孔径越大, 负载化疗药物的量越大。负载有阿霉素的AlOOH 纳米片呈现与pH有关的药物释放行为: 在pH~5的低pH 环境下快速释放, 而在pH~7.4 的近中性pH 下缓慢释放。流式细胞术显示, 相比于游离形式的阿霉素, 负载在AlOOH 纳米片上的阿霉素更易被癌细胞所吞噬。而且负载阿霉素后, 与低比表面积的AlOOH纳米片相比, 高比表面积的AlOOH 纳米片更有利于被癌细胞摄取、诱导癌细胞凋亡和坏死。因此, 本研究所合成的AlOOH 纳米片有望用作化疗药物递送体系。

关键词: 氢氧化铝, 纳米片, 癌症化疗, 存储, 药物输送

Abstract:

Alum has an excellent safety record and is the only licensed inorganic adjuvant for human vaccines. However, the exploration of alum nanosheets as chemotherapy drug delivery system, especially the clarification about the relationship between structures and drug loading properties, is totally insufficient. Herein, aluminum hydroxides (AlOOH) nanosheets with tunable specific surface area and pore size were synthesized by adjusting the synthesis time in the presence of triblock copolymers. The obtained materials exhibited the highest surface area about 470 m ²/g. The structure-dependent chemotherapy drug loading capability for AlOOH nanosheets was observed: the higher specific surface area and pore size are, the higher amount of chemotherapy drug is loaded. AlOOH nanosheets loaded with doxorubicin showed a pH-dependent sustained release behavior with quick release in low pH about 5 and slow release in pH around 7.4. Doxorubicin-loaded AlOOH nanosheets exhibited much higher cancer cellular uptake efficiency than that in free form by flow cytometry. Moreover, doxorubicin-loaded AlOOH nanosheets with high specific surface area showed an increased cellular uptake efficiency and enhanced ratios of apoptosis and necrosis, compared with those showing low specific surface area. Therefore, AlOOH nanosheets are promising materials as chemotherapy drug delivery system.

Key words: aluminum hydroxide, nanosheet, cancer chemotherapy, storage, drug delivery

中图分类号:

TQ174

LI Xia,SHENASHEN Mohamed A,MEKAWY Moataz,TANIGUCHI Akiyoshi,EI-SAFTY Sherif A. 氢氧化铝纳米片: 结构依赖性癌症化疗药物的储运[J]. 无机材料学报, 2020, 35(2): 250-256.

LI Xia,SHENASHEN Mohamed A,MEKAWY Moataz,TANIGUCHI Akiyoshi,EI-SAFTY Sherif A. Aluminum Hydroxide Nanosheets with Structure-dependent Storage and Transportation toward Cancer Chemotherapy[J]. Journal of Inorganic Materials, 2020, 35(2): 250-256.

图/表 5

Scheme 1 Formation of AlOOH NSs, loading of chemotherapy drugs onto NSs, and intravenous injection of the as-prepared NSs

Fig. 1 (A) Transmission electron micrograph images of Al-L (a) and Al-H (b, c); (B) Atomic force microscopy image of Al-H; (C) N2 sorption isotherms and pore size distribution curves of the samples; (D) XRD patterns of the samples; (E) The release curves of Dox for the AlOOH NSs

Fig. 2 (A) Confocal laser scanning micrographs of cellular uptake of Al-H/Dox samples by DU145 cells after coculture for 0.5 (a), 2.5 (b) and 24 h (c); (B) Histogram and (C) quantitative results of Dox cellular uptake efficiency (E%) by DU145 cells incubated for 2 h with (a) control, (b) Al-L/Dox at 5 μg/mL of particles, (c) Al-H/Dox at 5 μg/mL of particles, and (d) free Dox with an equivalent amount of Dox loaded onto Al-H/Dox samples

Fig. 3 Percentage of apoptosis and necrosis in DU145 cells treated with control (A), Al-L/Dox at 25 μg/mL (B), or Al-H/Dox at 25 μg/mL (C) for 1 d; Free Dox with an equivalent amount of Dox released from Al-H/Dox after 1 d at pH 5 was used as contrast (D)

Fig. 4 Blood biochemistry analysis (A-E) of mice after intravenous administration with Al-H (n=3)

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氢氧化铝纳米片: 结构依赖性癌症化疗药物的储运

Aluminum Hydroxide Nanosheets with Structure-dependent Storage and Transportation toward Cancer Chemotherapy

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