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Title: Catalase‐Functionalized Iron Oxide Nanoparticles Reverse Hypoxia‐Induced Chemotherapeutic Resistance
Abstract

Intratumoral hypoxia is a major contributor to multiple drug resistance (MDR) in cancer, and can lead to poor prognosis of patients receiving chemotherapy. Development of an MDR‐inhibitor that mitigates the hypoxic environment is crucial for cancer management and treatment. Reported is a biocompatible and biodegradable catalase‐conjugated iron oxide nanoparticle (Cat‐IONP) capable of converting reactive oxygen species to molecular oxygen to supply an oxygen source for the hypoxic tumor microenvironment. Cat‐IONP demonstrates initial enzymatic activity comparable to free catalase while providing a nearly threefold increase in long‐term enzymatic activity. It is demonstrated that Cat‐IONP significantly reduces the in vitro expression of hypoxia‐inducible factors at the transcription level in a breast cancer cell line. Co‐treatment of Cat‐IONP and paclitaxel (PTX) significantly increases the drug sensitivity of hypoxic‐cultured cells, demonstrating greater than twofold and fivefold reduction in cell viability in comparison to cells treated only with 80 and 120 × 10−6mPTX, respectively. These findings demonstrate the ability of Cat‐IONP to act as an MDR‐inhibitor at different biological levels, suggesting a promising strategy to combat cancer‐MDR and to optimize cancer management and treatment outcomes.

 
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NSF-PAR ID:
10459454
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Healthcare Materials
Volume:
8
Issue:
20
ISSN:
2192-2640
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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