cRGD-Peptide Modified Covalent Organic Frameworks for Precision Chemotherapy in Triple-Negative Breast Cancer

This study presents the use of nanoscale covalent organic frameworks (nCOFs) conjugated with tumor-targeting peptides for the targeted therapy of triple-negative breast cancer (TNBC). While peptides have previously been used for targeted delivery, their conjugation with COFs represents an innovative...

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Detalhes bibliográficos
Autores: Benyettou, Farah, Khair, Mostafa, Prakasam, Thirumurugan, Varghese, Sabu, Matouk, Zineb, Alkaabi, Maryam, Pena-Sánchez, Pilar, Boitet, Maylis, AbdulHalim, Rasha, Sharma, Sudhir Kumar, Ghemrawi, Rose, Thomas, Sneha, Whelan, Jamie, Pasricha, Renu, Jagannathan, Ramesh, Gándara Barragán, Felipe, Trabolsi, Ali
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/383654
Acesso em linha:http://hdl.handle.net/10261/383654
https://api.elsevier.com/content/abstract/scopus_id/85204061879
Access Level:acceso abierto
Palavra-chave:covalent organic frameworks (COFs)
integrin-targeting RGD peptides
pH-responsive nanoparticles
targeted drug delivery
triple-negative breast cancer (TNBC)
Descrição
Resumo:This study presents the use of nanoscale covalent organic frameworks (nCOFs) conjugated with tumor-targeting peptides for the targeted therapy of triple-negative breast cancer (TNBC). While peptides have previously been used for targeted delivery, their conjugation with COFs represents an innovative approach in this field. In particular, we have developed alkyne-functionalized nCOFs chemically modified with cyclic RGD peptides (Alkyn-nCOF-cRGD). This configuration is designed to specifically target αvβ3 integrins that are overexpressed in TNBC cells. These nCOFs exhibit excellent biocompatibility and are engineered to selectively disintegrate under acidic conditions, allowing for precise and localized drug release in tumor environment. Doxorubicin, a chemotherapeutic agent, has been encapsulated in these nCOFs with high loading efficiency. The therapeutic potential of Alkyn-nCOF-cRGD has been demonstrated in vitro and in vivo models. It shows significantly improved drug uptake and targeted cell death in TNBC, highlighting the efficacy of receptor-mediated endocytosis and pH-controlled drug release. This strategy leverages the unique properties of nCOFs with targeted drug delivery to achieve significant advances in personalized cancer therapy and set a new standard for precision chemotherapeutic delivery.