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

doi:10.15541/jim20190052

Abstract

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

CLC Number:

TQ174

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.

Figures/Tables 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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