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Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer
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Resumo(s)
Colorectal cancer (CRC) is a major global health concern, ranking among the most common
cancers and the third leading cause of cancer-related deaths. The high mortality associated with CRC is
attributed mainly to difficulties in early detection and the lack of effective targeted therapies. The
Transferrin receptor 1 (TfR1) is particularly attractive as a therapy target given its notable
overexpression in tumor cells, particularly in CRC. This study explored the potential of a nanoparticle
(NPs)-based drug delivery system targeting TfR1 to improve the precision and efficacy of CRC
treatment. First, we characterized three human colorectal cancer cell lines (SW480, HT-29, and
HCT116), a healthy human intestinal epithelial cell line (hIECs), and a murine CRC cell line (MC38)
using western blot and immunofluorescence assays to confirm TfR1 expression. Next, we engineered
NPs composed of poly (ethylene glycol) (PEG) and poly (lactic acid) (PLA), functionalized with the T7
peptide (HAIYPRH) to enhance their specificity for TfR1-expressing cells. Targeting efficiency of these
NPs was assessed across all cell lines by evaluating the cellular uptake using flow cytometry. Upon
establishing the optimal formulation for these NPs for TfR1-targeting, we encapsulated doxorubicin
(DOX) to evaluate their therapeutic potential. Both in vitro and in vivo studies were performed to assess
the efficacy of these DOX-loaded TfR1-targeted NPs. In vitro studies demonstrated selective delivery
of DOX to CRC cells, suggesting a marked reduction in off-target effects. In vivo studies in a murine
model of CRC further supported these findings, showing that DOX-loaded TfR1-targeted NPs
significantly improved survival rates and reduced tumor growth compared to free DOX or PBS
treatments. These results highlight the promise of TfR1-targeted NPs as a precise strategy for CRC
therapy, offering enhanced treatment efficacy while reducing systemic toxicity. This novel approach
could lead to the development of more targeted and less harmful cancer treatments.
Descrição
Tese de mestrado, Biologia Evolutiva e do Desenvolvimento , 2024, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
cancro colorretal recetor de transferrina nanopartículas polimersomas doxorubicina Teses de mestrado - 2024