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Arsenic trioxide (As2O3, ATO), a FDA approved drug for hematologic malignancies, was proved of efficient growth inhibition of cancer cell in vitro or solid tumor in vivo.However,its effect on solid tumor in vivo was hampered by its poor pharmacokinetics (PK) and dose-limited toxicity.In this study, a polyacrylic acid (PAA) capped pH-triggered mesoporous silica nanoparticles (MSN) was conducted to improve the pharmacokinetics and enhance the antitumor effect of ATO.The MSN loaded with ATO was grafted with PAA (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 on circulation.The nanoparticles was characterized with uniform grain size (particle sizes of 158.6 ± 1.3 nm and pore sizes of 3.71nm, respectively), historically comparable drug loading efficiency (11.42 ± 1.75%),pH-responsive and strengthened sustained release features.The cell toxicity of amino groups modified MSN (NH2-MSN) was significantly reduced by capping of PAA.In pharmacokinetics studies, the t1/2β Was prolonged by 1.3 times, and the area under curve (AUC) was increased by 2.6 times in PAA-ATO-MSN group compared with free ATO group.Subsequently, the antitumor efficacy in vitro (SMMC-7721 cell line) and in vivo (H22 xenografts) was remarkably enhanced indicated that PAA-ATO-MSN improved the antitumor effect of the drug.These results suggest that the PAA-MSN will be a promising nanocarrier for improving pharmacokinetics features and enhancing the anti-tumor efficacy of ATO.