Reversal Multidrug Resistance and Biodistribution of Targeted Nanoparticles Tf-Peg-PLL-PLGA Combined with Daunorubicin and Tetrandrine in Tumor-Bearing Nude Mice

Abstract

The study was to investigate the reversal multidrug resistance treatment and biodistribution of nanoparticles polyethylene glycol (PEG)-poly L-lysine (PLL)-poly lactic-co-glycolic acid (PLGA) (PEG-PLL-PLGA) modified by transferrin (Tf) combined with daunorubicin (DNR) and tetrandrine (Tet) in leukemia bearing nude mice model. Anti-tumor effect of nanoparticles in nude mice with K562/A02 resistant leukemia cell lines xenografts was observed. Subsequently, transcription and protein expression levels of transferrin receptor (TfR), P-glycoprotein (P-gp), MRP and NF-κB were determined by quantitative real-time polymerase chain reaction (quantitative real-time PCR) and Western blot analysis. DNR concentration in plasma, tumor tissue and major organs was detected by high performance liquid chromatography (HPLC). DNR-Tet-Tf-PEG-PLL-PLGA nanoparticles group significantly inhibited tumor, while the immunohistochemistry of tumor tissue displayed that the nanoparticles can induce apoptosis of tumor cells. Furthermore, DNR-Tet-Tf-PEG-PLL-PLGA group markedly increased TfR expression, and noticeably decreased P-gp, MRP and NF-kB expression. DNR concentration of tumor tissues in DNR-Tet-Tf-PEG-PLL-PLGA group injected by the tail vein was significantly higher than DNR-Tet-PEG-PLL-PLGA group. DNR-Tet-Tf-PEG-PLL-PLGA nanoparticles have the good ability to active targeting and reverse drug resistance, therefore provide a new initiative targeted therapy for cancer. DisclosuresNo relevant conflicts of interest to declare.