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Scientific Reports

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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.

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This work was partly supported by the National Institutes of Health (NIH) grants U01 HL111146 (K.N.), R01 HL118498 (K.N.), R21 1CA175879 (D.S.), Cancer Prevention & Research Institute of Texas [RP120670-C3 to D.S.] and the Department of Defense (DOD) grant W81XWH-11–1–0270 (D.S.).

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.

Department of Bioengineering, University of Texas at Arlington,


Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.