期刊
JOURNAL OF BIOMATERIALS APPLICATIONS
卷 31, 期 1, 页码 23-35出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/0885328216637211
关键词
pH-triggered MSN; arsenic trioxide; sustained release; pharmacokinetics; solid tumor
资金
- National Science Foundation of China [81274089, 81473361]
- Natural Science Foundation of Zhejiang Province [LZ13H280001, LY12H28004]
- Science and Technology Innovation Team Project of Zhejiang Province [2015R410051]
Arsenic trioxide (As2O3, ATO), a FDA approved drug for hematologic malignancies, was proved of efficient growth inhibition of cancer cell invitro or solid tumor invivo. However, its effect on solid tumor invivo was hampered by its poor pharmacokinetics and dose-limited toxicity. In this study, a polyacrylic acid capped pH-triggered mesoporous silica nanoparticles was conducted to improve the pharmacokinetics and enhance the antitumor effect of arsenic trioxide. The mesoporous silica nanoparticles loaded with arsenic trioxide was grafted with polyacrylic acid (PAA-ATO-MSN) as a pH-responsive biomaterial on the surface to achieve the release of drug in acidic microenvironment of tumor, instead of burst release action in circulation. The nanoparticles were characterized with uniform grain size (particle sizes of 158.6 +/- 1.3 nm and pore sizes of 3.71 nm, respectively), historically comparable drug loading efficiency (11.42 +/- 1.75%), pH-responsive and strengthened sustained release features. The cell toxicity of amino groups modified mesoporous silica nanoparticles (NH2-MSN) was significantly reduced by capping of polyacrylic acid. In pharmacokinetic studies, the half time (t(1/2)) was prolonged by 1.3 times, and the area under curve) was increased by 2.6 times in PAA-ATO-MSN group compared with free arsenic trioxide group. Subsequently, the antitumor efficacy invitro (SMMC-7721 cell line) and invivo (H22 xenografts) was remarkably enhanced indicated that PAA-ATO-MSN improved the antitumor effect of the drug. These results suggest that the polyacrylic acid capped mesoporous silica nanoparticles (PAA-MSN) will be a promising nanocarrier for improving pharmacokinetic features and enhancing the anti-tumor efficacy of arsenic trioxide.
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