| Title | Combined mTOR inhibitor rapamycin and doxorubicin-loaded cyclic octapeptide modified liposomes for targeting integrin alpha 3 in triple-negative breast cancer |
| Authors | Dai, Wenbing Yang, Fang Ma, Ling Fan, Yuchen He, Bing He, Qihua Wang, Xueqing Zhang, Hua Zhang, Qiang |
| Affiliation | Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. Peking Univ, Med & Hlth Analyt Ctr, Beijing 100191, Peoples R China. |
| Keywords | Triple-negative breast cancer Liposomal doxorubicin Targeting delivery Rapamycin Combined therapy INDUCIBLE FACTOR-I DRUG-COMBINATION TUMOR-CELLS EXPRESSION MDA-MB-231 RECEPTORS CARCINOMA APOPTOSIS THERAPY GROWTH |
| Issue Date | 2014 |
| Publisher | biomaterials |
| Citation | BIOMATERIALS.2014,35,(20),5347-5358. |
| Abstract | A novel therapeutic strategy combining mTOR inhibitor rapamycin (RAPA) and doxorubicin (DOX)-loaded cyclic octapeptide liposomes for targeting integrin alpha 3 was expected to combat the triple-negative breast cancer (TNBC). RAPA was loaded into PEG-PCL polymer micelles (M-RAPA) to realize solubilization. Flow cytometry analysis and laser confocal microscopy were used to evaluate the in vitro cellular uptake. The in vivo tumor targeting and bio-distribution were investigated by living fluorescence imaging. As the results, LXY modification significantly enhanced the cellular uptake of liposomal DOX in integrin alpha 3 overexpressed TNBC cells (MDA-MB-231) in vitro and accordingly improved the tumor accumulation of liposomes in vivo. When used alone or in combination with IXY-LS-DOX, M-RAPA could greatly inhibit the expression of HIF-1 alpha protein, which is always highly expressed in malignant cancers and involved in tumor angiogenesis, proliferation, therapeutic resistance and poor prognosis. Meanwhile, the improved efficacy of combined targeted therapy with LXY-LS-DOX and M-RAPA was demonstrated by the in vitro cytotoxicity against model TNBC cells and in vivo anti-tumor activity against mouse bearing TNBC model. These results suggested that the targeted combinational therapy based on LXY-LS-DOX and M-RAPA systems may provide a rational strategy to improve therapeutic outcomes of TNBC. (c) 2014 Elsevier Ltd. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/156359 |
| ISSN | 0142-9612 |
| DOI | 10.1016/j.biomaterials.2014.03.036 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
