Magnetically driven drug delivery systems improving targeted immunotherapy for colon-rectal cancer

Renata Grifantini, Monia Taranta, Lisa Gherardini, Ilaria Naldi, Matteo Parri, Alberto Grandi, Ambra Giannetti, Sara Tombelli, Gioia Lucarini, Leonardo Ricotti, Susanna Campagnoli, Elisa De Camilli, Gualtiero Pelosi, Francesco Baldini, Arianna Menciassi, Giuseppe Viale, Piero Pileri, Caterina Cinti

Research output: Contribution to journalArticle

Abstract

Colorectal cancer (CRC) is one of the major causes of cancer-associated mortality worldwide. The currently approved therapeutic agents show a rather limited efficacy. We have recently demonstrated that the atypical cadherin FAT1 is a specific marker of CRC and that the FAT1-specific monoclonal antibody mAb198.3 may offer new therapeutic opportunities for CRC, being efficiently internalized by cancer cells and reducing cancer growth in colon cancer xenograft models. In this study we explored the therapeutic efficacy of mAb198.3 using two drug delivery systems (DDS) for improving the targeted treatment of CRC. The mAb198.3 was either directly bound to super-paramagnetic nanoparticles (spmNPs) or embedded into human erythrocyte-based magnetized carriers, named Erythro-Magneto-Hemagglutinin Virosomes (EMHVs) to produce two different novel mAb198.3 formulations. Both DDS were endowed with magnetic properties and were anchored in the target tumor site by means of an external permanent magnet. The antibody loading efficiency of these two magnetically driven drug delivery systems and the overall therapeutic efficacy of these two formulations were assessed both in vitro and in a proof-of-concept in vivo study. We demonstrated that mAb198.3 bound to spmNPs or embedded into EMHVs was very effective in targeting FAT1-positive colon cancer cells in vitro and accumulating in the tumor mass in vivo. Although both in vivo administered mAb198.3 formulations have approximately 200 lower antibody doses needed, these showed to achieve a relevant therapeutic effect, thus reducing cancer growth more efficiently respect to the naked antibody. These results indicate that the two proposed magnetically driven drug delivery systems have a considerable potential as platforms to improve bioavailability and pharmacodynamics of anti-FAT mAb198.3 and raise new opportunities for a targeted therapy of CRC.

Original languageEnglish
Pages (from-to)76-86
Number of pages11
JournalJournal of Controlled Release
Volume280
DOIs
Publication statusPublished - Jun 28 2018

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Keywords

  • Colorectal cancer
  • Magnetic delivery system
  • Monoclonal antibody
  • Nanoparticles
  • Targeting

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Grifantini, R., Taranta, M., Gherardini, L., Naldi, I., Parri, M., Grandi, A., Giannetti, A., Tombelli, S., Lucarini, G., Ricotti, L., Campagnoli, S., De Camilli, E., Pelosi, G., Baldini, F., Menciassi, A., Viale, G., Pileri, P., & Cinti, C. (2018). Magnetically driven drug delivery systems improving targeted immunotherapy for colon-rectal cancer. Journal of Controlled Release, 280, 76-86. https://doi.org/10.1016/j.jconrel.2018.04.052