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 trans-activator of transcription (TAT) peptide were designed for treatment of cervical cancer v...

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Bibliographic Details
Published in:Journal of controlled release 2021-08, Vol.336, p.572-582
Main Authors: Lv, Fengmei, Wang, Jun, Chen, Haini, Sui, Li, Feng, Linglin, Liu, Zhepeng, Liu, Yu, Wei, Gang, Lu, Weiyue
Format: Article
Language:English
Subjects:
Cervical cancer
Docetaxel
Nanocrystal
TAT
Vaginal administration
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Summary: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 trans-activator 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 mucosa-related diseases by vaginal administration. [Display omitted] •PEGylation endowed docetaxel nanocrystals with good stability and minimized interaction with mucin.•TAT modification favored mucosal penetration of docetaxel nanocrystals.•Vaginally-administered TAT-modified PEGylated docetaxel nanocrystals efficiently inhibited the growth of orthotopic model cervicovaginal tumors.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2021.07.008