TY - JOUR
T1 - cRGD-Peptide Modified Covalent Organic Frameworks for Precision Chemotherapy in Triple-Negative Breast Cancer
AU - Benyettou, Farah
AU - Khair, Mostafa
AU - Prakasam, Thirumurugan
AU - Varghese, Sabu
AU - Matouk, Zineb
AU - Alkaabi, Maryam
AU - Pena-Sánchez, Pilar
AU - Boitet, Maylis
AU - AbdulHalim, Rasha
AU - Sharma, Sudhir Kumar
AU - Ghemrawi, Rose
AU - Thomas, Sneha
AU - Whelan, Jamie
AU - Pasricha, Renu
AU - Jagannathan, Ramesh
AU - Gándara, Felipe
AU - Trabolsi, Ali
N1 - Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.
PY - 2024/10/23
Y1 - 2024/10/23
N2 - 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.
AB - 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.
KW - covalent organic frameworks (COFs)
KW - integrin-targeting RGD peptides
KW - pH-responsive nanoparticles
KW - targeted drug delivery
KW - triple-negative breast cancer (TNBC)
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UR - http://www.scopus.com/inward/citedby.url?scp=85204061879&partnerID=8YFLogxK
U2 - 10.1021/acsami.4c10812
DO - 10.1021/acsami.4c10812
M3 - Article
C2 - 39267454
AN - SCOPUS:85204061879
SN - 1944-8244
VL - 16
SP - 56676
EP - 56695
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 42
ER -