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

Authors :
Benyettou F
Khair M
Prakasam T
Varghese S
Matouk Z
Alkaabi M
Pena-Sánchez P
Boitet M
AbdulHalim R
Sharma SK
Ghemrawi R
Thomas S
Whelan J
Pasricha R
Jagannathan R
Gándara F
Trabolsi A
Source :
ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2024 Oct 23; Vol. 16 (42), pp. 56676-56695. Date of Electronic Publication: 2024 Sep 13.
Publication Year :
2024

Abstract

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 α <subscript>v</subscript> β <subscript>3</subscript> 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.

Details

Language :
English
ISSN :
1944-8252
Volume :
16
Issue :
42
Database :
MEDLINE
Journal :
ACS applied materials & interfaces
Publication Type :
Academic Journal
Accession number :
39267454
Full Text :
https://doi.org/10.1021/acsami.4c10812