Targeted co-delivery of docetaxel, cisplatin and herceptin by vitamin E TPGS-cisplatin prodrug nanoparticles for multimodality treatment of cancer

摘要

We developed a nanocarrier system of herceptin-conjugated nanoparticles of D-alpha-tocopheryl-co-poly(ethylene glycol) 1000 succinate (TPGS)-cisplatin prodrug (HTCP NPs) for targeted co-delivery of cisplatin, docetaxel and herceptin for multimodality treatment of breast cancer of high human epidermal growth factor receptor 2 (HER2) overexpression. Co-polymers poly(lactic acid)-TPGS (PLA-TPGS) and carboxyl group-terminated TPGS (TPGS-COOH) were also added in the polymeric matrix to stabilize the prodrug nanoparticles and to facilitate herceptin conjugation. The HTCP NPs of high, moderate and low docetaxel versus cisplatin ratio were prepared by the nanoprecipitation method, which showed a pH-sensitive release for both anticancer drugs. The therapeutic effects of HTCP NPs were evaluated in vitro and compared with Taxotere? and cisplatin. The HTCP NPs of high docetaxel versus cisplatin ratiowere found to have better efficacy than those ofmoderate and lowdocetaxel versus cisplatin ratio. The targeting effects of the HTCP NPs were demonstrated by a much lower IC_(50) value of 0.0201+0.00780+0.1629 μg/mL of docetaxel+cisplatin+herceptin for SK-BR-3 cells, which are of high HER2 overexpression, than that of 0.225+0.0875+1.827 μg/mL for NIH_3T3 cells,which are of lowHER2 overexpression, after 24 h incubation. The same design of TPGS prodrug nanoparticles can also be applied for targeted co-delivery of other hydrophilic and hydrophobic drugs.