Specific targeting of tumor cells by lyophilisomes functionalized with antibodies

Etienne van Bracht, Sarah Stolle, Theo G. Hafmans, Otto C. Boerman, Egbert Oosterwijk, Toin H. van Kuppevelt, Willeke F. Daamen*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    11 Citations (Scopus)

    Abstract

    Lyophilisomes are a novel class of proteinaceous biodegradable nano/micro drug delivery capsules prepared by freezing, annealing and Iyophilization. In the present study, lyophilisomes were functionalized for active targeting by antibody conjugation in order to obtain a selective drug-carrier system.

    Lyophilisomes were vapor crosslinked for 2 h, resulting in stable capsules, while leaving sufficient primary amines for further modification. The humanized KC4 (hKC4) antibody was conjugated to lyophilisomes to achieve specific targeting to mucin 1 (MUC1)-overexpressing tumor cells. For this, thiolated antibodies were conjugated to maleimide-activated lyophilisomes, resulting in an hKC4 specific drug targeting system toward MUC1-overexpressing human ovarian and cervical tumor cells. FACS analysis demonstrated that hKC4-conjugated lyophilisomes bound specifically to MUC1-overexpressing tumor cells (HeLa, OVCAR-3, and SKOV-3 cells), compared to MUC1-negative cells (LS174T). In addition, control non-specific IgG-conjugated lyophilisomes did not bind to MUC1-overexpressing tumor cells. When MUC1-positive and -negative cells were combined in one culture, hKC4-conjugated lyophilisomes specifically targeted MUC1-positive cells, whereas negative cells showed merely background levels. Transmission electron microscopy showed uptake of hKC4-conjugated lyophilisomes via phagocytosis or macropinocytosis.

    In conclusion, hKC4-conjugated albumin-based lyophilisomes represent a potential drug delivery system for targeted drug transport to MUC1-overexpressing tumor cells. (C) 2014 Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)80-89
    Number of pages10
    JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
    Volume87
    Issue number1
    DOIs
    Publication statusPublished - May-2014

    Keywords

    • Drug delivery
    • Albumin
    • MUC1
    • hKC4 antibody
    • Tumor targeting
    • Nano/micro particles
    • Internalization
    • DRUG-DELIVERY
    • CONJUGATED NANOPARTICLES
    • CONTRAST AGENT
    • CANCER
    • ALBUMIN
    • THERAPEUTICS
    • OPTIMIZATION
    • HYDROLYSIS
    • PACLITAXEL
    • EFFICACY

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