Publication

Specific targeting of tumor cells by lyophilisomes functionalized with antibodies

van Bracht, E., Stolle, S., Hafmans, T. G., Boerman, O. C., Oosterwijk, E., van Kuppevelt, T. H. & Daamen, W. F., May-2014, In : European Journal of Pharmaceutics and Biopharmaceutics. 87, 1, p. 80-89 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

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

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
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

ID: 16107444