Development of low molecular weight heparin based nanoparticles for metastatic breast cancer therapy

Tumor metastasis is the primary obstacle in cancer treatment and is always the leading cause of human death. And heparin and its derivatives are potential anti-metastatic agents with good biocompatibility. In this work, low molecular weight heparin (LMWH) based LMWH-Cholesterol (LHC) conjugates were prepared for intravenous delivery of doxorubicin (DOX). The DOX/LHC nanoparticles (DOX/LHC NPs) exhibited a spherical shape with a mean diameter of 135.5 ± 2.2 nm and had a longer circulation time than that of DOX. The in vitro results confirmed that the DOX/LHC NPs was more effectively taken up by 4T1 cells and showed a stronger anti-metastatic effect by cell invasion and cell migration compared with DOX. Meanwhile, DOX/LHC NPs also exhibited superior anti-metastatic effects in the pulmonary metastasis model compared with other groups. The reason may be account for the synergistic effect between the cytotoxic drug of DOX and its drug carrier of LMWH based nanoparticles, which is capable of anti-metastatic and anti-angiogenic efficiency. Thus DOX/LHC nanoparticles could be a promising anti-metastatic drug delivery system for postoperative chemotherapy.