Transferrin conjugated poly (γ-glutamic acid-maleimide-co-L-lactide)-1,2-dipalmitoylsn-glycero-3-phosphoethanolamine copolymer nanoparticles for targeting drug delivery

Abstract

Targeted drug delivery strategies have shown great potential in solving some problems of chemotherapy, such as non-selectivity and severe side effects, thus enhancing the anti-tumor efficiency of chemotherapeutic agents. In this work, we have prepared a novel nanoparticle consisted of amphiphilic poly(γ-glutamic acid-maleimide-co-L-lactide)-1,2-dipalmitoylsn-glycero-3-phosphoethanolamine (γ-PGA-MAL-PLA-DPPE) copolymer decorated with transferrin (Tf), which can specifically deliver anti-cancer drug paclitaxel (PTX) to the tumor cells for targeting chemotherapy. These nanoparticles (NPs) have preferable particle size, high encapsulation efficiency and a pH-dependent release profile. As expected, The Tf modification mediate specific targeting to nasopharyngeal carcinoma (C666-1) cells and human cervical carcinoma (Hela) cells with the transferrin receptor (TfR) overexpressed and enhance cellular uptake of the NPs, as demonstrated by flow cytometry and confocal microscopy assays. In vitro cytotoxicity studies reveal that the NPs have excellent biocompatibility, and the presence of Tf enhance the activity of PTX to the targeted cells. All these results prove that Tf modified γ-PGA-MAL-PLA-DPPE NPs could facilitate the tumor-specific therapy. Therefore, such a targeting drug delivery system provides significant advances toward cancer therapy.

Keywords: 1,2-Dipalmitoylsn-glycero-3-phosphoethanolamine; Amphiphilic copolymer; Paclitaxel; Poly γ-glutamic acid; Targeting delivery system; Transferrin.