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

• We designed a novel paclitaxel (PTX)-loaded copolymer nanoparticles based on transferrin (Tf) decorated poly(γ-glutamic acid-maleimide-co-L-lactide)-1,2-dipalmitoylsn-glycero-3-phosphoethanolamine (γ-PGA-MAL-PLA-DPPE).
• The preferable particle size, high encapsulated efficiency and a pH-dependent release profile have been successfully achieved.
• Flow cytometry and CLSM images indicated that surface modification of Tf on PTX-loaded NPs further led to enhanced intracellular uptake of both C666-1 cells and Hela cells via specific ligand-receptor interaction.
• The results indicated that the targeting PTX-Tf-NPs had more advantages in targeted tumor therapy.

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.

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