Validation of a novel hybrid nanosystem integrating cytotoxic and magnetic properties as a tool to potentiate the antitumor activity

• Autor(a) principal: Azevedo, Afonso Toledo
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/163876
• topic: Colon cancer; 5-fluorouracil (5-FU); liposomes; iron oxide nanoparticles (MNPs); antiproliferative activity; magnetic properties; Domínio/Área Científica::Engenharia e Tecnologia::Nanotecnologia

Colon cancer (CC) is the fourth most frequent type of cancer and the fifth leading cause of cancer-related deaths worldwide. The majority of cases are diagnosed at a later stage, leading to the need for more aggressive treatments such as chemotherapy. 5-Fluorouracil (5-FU), known for its cytotoxic prop-erties against tumor cells, has emerged as a viable chemotherapeutic agent. However, it presents several drawbacks such as lack of specificity or short half-life. To reduce these drawbacks, the chemotherapeu-tic compound can be incorporated into drug delivery systems (DDS), allowing longer circulation times and preferential targeting and release at the tumor sites. The current research was focused on the devel-opment of a hybrid delivery system, combining both therapeutic and magnetic properties. For this pur-pose, 5-FU was loaded in long blood circulation liposomes (DMPC:Chol:DSPE-PEG) simultaneously with iron oxide nanoparticles (MNPs). Remote loading was found to be the best method for incorporat-ing 5-FU in nanoliposomes by establishing an ammonium sulphate gradient. Unloaded liposomes were prepared by the dehydration-rehydration technique, followed by an extrusion step to reduce and homog-enize their mean size followed by a gel filtration to establish the ammonium sulfate gradient. The char-acterization of the developed nanoformulations was done in terms of incorporation parameters, mean size and surface charge. In vitro studies confirmed that 5-FU antiproliferative activity, towards a murine colon cancer (CT-26) cell line, was preserved after incorporation in liposomes while the MNPs did not exhibit cytotoxic properties. Additionally, the presence of MNPs was shown to confer magnetic prop-erties to the liposomes, allowing them to respond to external magnetic fields. Moreover, the liposomal formulations were characterized by transmission electron microscopy (TEM). In sum, a lipid nanosys-tem loading a chemotherapeutic agent and displaying magnetic characteristics was successfully de-signed and physiochemically characterized, for further in vivo applications.