Effectiveness of a Controlled 5-FU Delivery Based on FZD10 Antibody-Conjugated Liposomes in Colorectal Cancer In vitro Models

Abstract

<jats:p>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.</jats:p>

Antibody‐Incorporated Nanomedicines for Cancer Therapy

“…Additionally, anti‐FZD antibodies can be utilized for the targeted drug delivery to FZD + cancer cells. [ 632 ] For instance, Ruenraroengsak et al functionalized MSN–ZnO–AuNSs (which were star‐shaped AuNPs coated by ZnO nanoparticles with a mesoporous silica nanolayer) with anti‐FZD7 antibodies to afford FZD7–MSN–ZnO–AuNSs for treating HER2 + breast cancer cells, TNBC cells, and drug‐resistant breast cancer cells. [ 633 ] Owing to the conjugation with the anti‐FZD7 antibody, the FZD7–MSN–ZnO–AuNSs efficiently reduced the viability of all the investigated cell lines and showed improved toxicity against the drug‐resistant cell line that had the highest level of FZD7 expression.…”

Advancements in Rectal Drug Delivery Systems: Clinical Trials, and Patents Perspective

“…In a study, 5-fluorouracil liposomes were prepared and evaluated in vitro on cell lines. Results showed an enhanced cytotoxic effect of 5-fluorouracil as compared to pure 5-fluorouracil and found to potential carriers for rectal administration [ 93 ].…”

The Construction of Immunoliposomes (Review)

“…Процедура сочетания включает двухстадийную карбоимидную реакцию: после очистки липосом карбоксильную группу активируют добавлением N-(3-диметиламинопропил)-N'-этилкарбодиимида (EDC) и N-гидроксисульфосукцинимида (сульфо-NHS), смесь инкубируют при комнатной температуре и затем ультрацентрифугируют или хроматографируют для удаления избытка сшивающих реагентов. Промежуточный продукт на основе сложного эфира сульфо-NHS, реагирующего с амином, обладает достаточной стабильностью, чтобы обеспечить связывание с АТ [65,66].…”