Enhanced mucosal penetration and efficient inhibition efficacy against cervical cancer of PEGylated docetaxel nanocrystals by TAT modification

To investigate the potential of cell penetrating peptide (CPP) modification on nanomedicine for improving mucosal penetration and effective therapy of cervical cancer, docetaxel nanocrystals modified with transactivator of transcription (TAT) peptide were designed for treatment of cervical cancer via vaginal administration. Docetaxel nanocrystals were coated by polymerization of dopamine to form polydopamine (PDA) coating which facilitated TAT modification and PEGylation for less mucus entrapment to get PEGylated nanocrystals modified with TAT (NC@PDA-PEG-TAT). Enhanced cellular drug uptake and cytotoxicity of NC@PDA-PEG-TAT was observed in cervical cancer-related TC-1 cells than that of PEGylated nanocrystals (NC@PDA-PEG). Intravaginally administered NC@PDA-PEG-TAT dispersed in poloxamer 407-based thermosensitive gel exhibited prolonged in vivo intravaginal retention, deeper mucosal penetration and more potent inhibition on the growth of murine orthotopic cervical cancer than NC@PDA-PEG, PDA-coated nanocrystals or unmodified nanocrystals. All data suggested the significance of CPP-modification on nanocrystals in the local treatment of vaginal mucosarelated diseases by vaginal administration.

Automated summary

Cell penetrating peptide (CPP) modification on docetaxel nanocrystals significantly improved mucosal penetration and therapeutic efficacy for cervical cancer via vaginal administration. The PEGylated nanocrystals modified with TAT showed enhanced cellular uptake and cytotoxicity in cervical cancer cells, indicating its potential for local treatment of vaginal mucosa-related diseases.