Effectiveness of a controlled 5-fu delivery based on fzd10 antibody-conjugated liposomes in colorectal cancer in vitro models

Maria Principia Scavo, Annalisa Cutrignelli, Nicoletta Depalo, Elisabetta Fanizza, Valentino Laquintana, Giampietro Gasparini, Gianluigi Giannelli, Nunzio Denora

Research output: Contribution to journalArticlepeer-review

Abstract

The use of controlled delivery therapy in colorectal cancer (CRC) reduces toxicity and side effects. Recently, we have suggested that the Frizzled 10 (FZD10) protein, a cell surface receptor belonging to the FZD protein family that is overexpressed in CRC cells, is a novel candidate for targeting and treatment of CRC. Here, the anticancer effect of novel immuno-liposomes loaded with 5-Fluorouracil (5-FU), decorated with an antibody against FZD10 (anti-FZD10/5-FU/LPs), was evaluated in vitro on two different CRC cell lines, namely metastatic CoLo-205 and nonmetastatic CaCo-2 cells, that were found to overexpress FZD10. The anti-FZD10/5-FU/LPs obtained were extensively characterized and their preclinical therapeutic efficacy was evaluated with the MTS cell proliferation assay based on reduction of tetrazolium compound, scratch test, Field Emission Scanning Electron Microscopes (FE-SEM) investigation and immunofluorescence analysis. The results highlighted that the cytotoxic activity of 5-FU was enhanced when encapsulated in the anti-FZD10 /5-FU/LPs at the lowest tested concentrations, as compared to the free 5-FU counterparts. The immuno-liposomes proposed herein possess a great potential for selective treatment of CRC because, in future clinical applications, they can be encapsulated in gastro-resistant capsules or suppositories for oral or rectal delivery, thereby successfully reaching the intestinal tract in a minimally invasive manner.

Original languageEnglish
Article number650
Pages (from-to)1-19
Number of pages19
JournalPharmaceutics
Volume12
Issue number7
DOIs
Publication statusPublished - Jul 2020

Keywords

  • Colon cancer therapy
  • FZD10 protein
  • Liposomes
  • Target delivery nanosystem

ASJC Scopus subject areas

  • Pharmaceutical Science

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