Preparation and in vitro evaluation of arsenic trioxide-loaded phospholipid-capped mesoporous silica nanoparticles modified with Angiopep-2 as targeting drug delivery system / 中草药

ABSTRACT

Objective: To enhance the blood-brain barrier (BBB) penetration and glioma targeting ability of arsenic trioxide (As2O3), the lipid-coated mesoporous silica nanoparticles (MSN) modified with Angiopep-2 and polyacrylic acid (ANG-PAA-LP-MSN) is prepared by thin-film hydration method. This complex is specifically recognized and bound between ANG and low-density lipoprotein receptor-related protein-1 (LRP-1) which is highly expressed on BBB and glioma cells. Methods: The drug delivery system characterization were analysed by transmission electron microscopy (TEM) and thermogravimetric analysis (TGA). Dialysis bag method was used to analyse the drug release characteristics at different pH conditions (pH 6.0 and 7.4, respectively). Cytotoxicity of nanocarriers and the antitumor activity in vitro of this drug delivery system were measured on human brain micro-capillary endothelial cells (HBMEC) and glioma cells (C6) by MTT assay. Moreover, in vitro cells model of BBB was established to study the effect of vehicle on the transmembrane transport of As2O3. Results: The drug delivery system (ANG-PAA-LP-MSN@As2O3) was constructed successfully, it showed a rounded "core-shell" structure with good dispersibility and stability. The drug loading efficency was 6.32%. After PAA modification, this drug delivery system showed higher pH responsiveness to release medium, and the burst release of As2O3 was significantly reduced compared with that of unmodified group. Lipid coating could significantly improve the biosafety and penetration ability of BBB. The antitumor activity study showed that ANG-PAA-LP-MSN@As2O3 exhibited an ideal glioma inhibition effect in vitro. Conclusion: This smart targeting drug delivery system enhance the BBB penetration ability of As2O3, and the special pH responsiveness demonstrated antitumor ability through increasing its accumulation in the tumor site.