Catalase-Functionalized Iron Oxide Nanoparticles Reverse Hypoxia-Induced Chemotherapeutic Resistance.
Tin-Yo YenZachary R StephenGuanyou LinQingxin MuMike JeonStela UntoroParker WelshMiqin ZhangPublished in: Advanced healthcare materials (2019)
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 × 10-6 m PTX, 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.
Keyphrases
- poor prognosis
- papillary thyroid
- squamous cell
- multidrug resistant
- reactive oxygen species
- induced apoptosis
- long non coding rna
- iron oxide
- drug delivery
- lymph node metastasis
- signaling pathway
- photodynamic therapy
- mass spectrometry
- iron oxide nanoparticles
- transcription factor
- electronic health record
- quantum dots
- newly diagnosed
- binding protein
- adverse drug
- pi k akt