Research Article


2017, 10(3): 856–875


Paclitaxel-loaded hollow-poly(4-vinylpyridine) nano-particles enhance drug chemotherapeutic efficacy in lung and breast cancer cell lines

Rafael Contreras-Cáceres1, María C. Leiva2,3,4, Raúl Ortiz2,5, Amelia Díaz1, Gloria Perazzoli2, Miguel A. Casado-Rodríguez1, Consolación Melguizo2,3,4 (*), Jose M. Baeyens6, Juan M. López-Romero1,§, and Jose Prados2,3,4,§

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1 Department of Organic Chemistry, Faculty of Science, University of Málaga, 29071 Málaga, Spain
2 Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
3 Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
4 Biosanitary Institute of Granada (IBS. GRANADA), SAS-Universidad de Granada, 18014 Granada, Spain
5 Department of Health Science, University of Jaén, 23071 Jaén, Spain
6 Department of Pharmacology, Institute of Neuroscience, Biomedical Research Center (CIBM), University of Granada, 18100 Granada, Spain
§ These authors contributed equally to this work.

Keywords: paclitaxel, poly(4-vinylpyridine) (p4VP) nanoparticles, lung cancer, breast cancer, cytotoxicity, multicellular tumor spheroids
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ABSTRACT Paclitaxel (PTX), one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work, hollow-poly(4-vinylpyridine) (hollow-p4VP) nanoparticles (NPs) have been used for the first time to generate PTX@p4VP NPs, employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated. The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood (no hemolysis) and cell cultures (no cytotoxicity). Interestingly, PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung (A-549) and breast (MCF-7) cancer cells with a significant reduction of PTX IC50 (from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7). In addition, PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids (MTS), an in vitro system that mimics in vivo tumors, in comparison to free PTX. This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis, especially in lung cancer MTS. Our results offer the first evidence that hollowp4VP NPs can improve the antitumoral activity of PTX. This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.
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Paclitaxel-loaded hollow-poly(4-vinylpyridine) nano-particles enhance drug chemotherapeutic efficacy in lung and breast cancer cell lines. Nano Res. 2017, 10(3): 856–875

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