Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer

Bibliographic Details
Main Author: Pina, Ariana Santos
Publication Date: 2024
Format: Master thesis
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10400.5/97118
Summary: Tese de mestrado, Biologia Evolutiva e do Desenvolvimento , 2024, Universidade de Lisboa, Faculdade de Ciências
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spelling Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancercancro colorretalrecetor de transferrinananopartículaspolimersomasdoxorubicinaTeses de mestrado - 2024Departamento de Biologia AnimalTese de mestrado, Biologia Evolutiva e do Desenvolvimento , 2024, Universidade de Lisboa, Faculdade de CiênciasColorectal 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.Matias, DianaCarlos, Ana Rita Cabral Martins, 1985-Repositório da Universidade de LisboaPina, Ariana Santos202420242025-12-26T00:00:00Z2024-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.5/97118TID:203878825enginfo:eu-repo/semantics/embargoedAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T16:31:39Zoai:repositorio.ulisboa.pt:10400.5/97118Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T04:18:14.862460Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer
title Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer
spellingShingle Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer
Pina, Ariana Santos
cancro colorretal
recetor de transferrina
nanopartículas
polimersomas
doxorubicina
Teses de mestrado - 2024
Departamento de Biologia Animal
title_short Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer
title_full Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer
title_fullStr Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer
title_full_unstemmed Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer
title_sort Transferrin Receptor 1-targeted nanoparticle therapy for Colorectal Cancer
author Pina, Ariana Santos
author_facet Pina, Ariana Santos
author_role author
dc.contributor.none.fl_str_mv Matias, Diana
Carlos, Ana Rita Cabral Martins, 1985-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Pina, Ariana Santos
dc.subject.por.fl_str_mv cancro colorretal
recetor de transferrina
nanopartículas
polimersomas
doxorubicina
Teses de mestrado - 2024
Departamento de Biologia Animal
topic cancro colorretal
recetor de transferrina
nanopartículas
polimersomas
doxorubicina
Teses de mestrado - 2024
Departamento de Biologia Animal
description Tese de mestrado, Biologia Evolutiva e do Desenvolvimento , 2024, Universidade de Lisboa, Faculdade de Ciências
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024-01-01T00:00:00Z
2025-12-26T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.5/97118
TID:203878825
url http://hdl.handle.net/10400.5/97118
identifier_str_mv TID:203878825
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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