▎ 摘　　要

In this study, heparin and polyethyleneimine-folic acid modified graphene oxide was designed and synthesized as a dual-targeting biomaterial to load doxorubicin (DOX@GPFH) with high loading capacity for enhanced cellular uptake. GDC0941, a phosphatidylinositide 3-kinase/Akt phosphorylation inhibitor, was selected to enhance anti-metastasis effect of DOX@GPFH via down-regulating expression of matrix metalloproteinase. Modified with heparin, the stability of DOX@GPFH was significantly enhanced and the drug loading ratio increased largely from 64.4% to 125.1%. The inhibition rates of the mixture of DOX@GPFH and GDC0941 in vitro by wound healing, cell migration and invasion assays were 61.2% +/- 13.9%, 81.0% +/- 3.6% and 76.8% +/- 5.2%, respectively, while the tumor and the pulmonary anti-metastasis rates tested in vivo were 77.0% +/- 7.6% and 73.7% +/- 9.6%, respectively. Our findings illustrated an effective approach for developing dual-targeting graphene oxide with high drug loading for pulmonary anti-metastasis of breast cancer. (C) 2018 Elsevier Inc. All rights reserved.