Document Type
Article
Source Publication Title
Scientific Reports
First Page
1
Last Page
13
DOI
https://doi.org/10.1038/s41598-017-13320-4
Abstract
Late-stage diagnosis of lung cancer occurs ~95% of the time due to late manifestation of its symptoms, necessitating rigorous treatment following diagnosis. Existing treatment methods are limited by lack of specificity, systemic toxicity, temporary remission, and radio-resistance in lung cancer cells. In this research, we have developed a folate receptor-targeting multifunctional dual drug-loaded nanoparticle (MDNP) containing a poly(N-isopropylacrylamide)-carboxymethyl chitosan shell and poly lactic-coglycolic acid (PLGA) core for enhancing localized chemo-radiotherapy to effectively treat lung cancers. The formulation provided controlled releases of the encapsulated therapeutic compounds, NU7441 - a potent radiosensitizer, and gemcitabine - an FDA approved chemotherapeutic drug for lung cancer chemo-radiotherapy. The MDNPs showed biphasic NU7441 release and pH-dependent release of gemcitabine. These nanoparticles also demonstrated good stability, excellent hemocompatibility, outstanding in vitro cytocompatibility with alveolar Type I cells, and dose-dependent caveolaemediated in vitro uptake by lung cancer cells. In addition, they could be encapsulated with superparamagnetic iron oxide (SPIO) nanoparticles and visualized by MRI in vivo. Preliminary in vivo results demonstrated the low toxicity of these particles and their use in chemo-radiotherapy to effectively reduce lung tumors. These results indicate that MDNPs can potentially be used as nanovehicles to provide simultaneous chemotherapy and radiation sensitization for lung cancer treatment.
Disciplines
Biomedical Engineering and Bioengineering | Engineering
Publication Date
10-16-2017
Language
English
License
This work is licensed under a Creative Commons Attribution 3.0 License.
Recommended Citation
Menon, Jyothi Unnikrishna; Kuriakose, Aneetta; Iyer, Roshni; Hernandez, Elizabeth; Gandee, Leah; Zhang, Shanrong; Takahashi, Masaya; Zhang, Zhang; Saha, Debabrata; and Nguyen, Kytai Truong, "Dual-Drug Containing Core-Shell Nanoparticles for Lung Cancer Therapy" (2017). Bioengineering Faculty Publications. 21.
https://mavmatrix.uta.edu/bioengineering_facpub/21
Comments
The authors would also like to acknowledge Dr. Mingyuan Wei for his help with LCST measurements and the Molecular Pathology Core at the University of Texas Southwestern Medical Center at Dallas for the assistance with histology studies.