TY - JOUR
T1 - Effectiveness of a controlled 5-fu delivery based on fzd10 antibody-conjugated liposomes in colorectal cancer in vitro models
AU - Scavo, Maria Principia
AU - Cutrignelli, Annalisa
AU - Depalo, Nicoletta
AU - Fanizza, Elisabetta
AU - Laquintana, Valentino
AU - Gasparini, Giampietro
AU - Giannelli, Gianluigi
AU - Denora, Nunzio
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Colon cancer therapy
KW - FZD10 protein
KW - Liposomes
KW - Target delivery nanosystem
UR - http://www.scopus.com/inward/record.url?scp=85088485650&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088485650&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics12070650
DO - 10.3390/pharmaceutics12070650
M3 - Article
AN - SCOPUS:85088485650
VL - 12
SP - 1
EP - 19
JO - Pharmaceutics
JF - Pharmaceutics
SN - 1999-4923
IS - 7
M1 - 650
ER -