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

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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 hollow-p4VP 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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Acknowledgements

This research was funded by FEDER, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+i), by the Consejería de Salud de la Junta de Andalucía through projects (Nos. PI-0476-2016 and P11-CTS-7649). We also thank the financial support of CICYT, Spain, Project CTQ13-48418-P, FEDER funds. R. C.-C. acknowledges the Andalucía Tech program “U-mobility” co-financed by the University of Málaga and the European Community’s Seventh Framework Program (No. 246550). We thank the research grant (FPU) from Ministerio de Educacion Cultura y Deporte.

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Authors and Affiliations

  1. Department of Organic Chemistry, Faculty of Science, University of Málaga, 29071, Málaga, Spain

    Rafael Contreras-Cáceres, Amelia Díaz, Miguel A. Casado-Rodríguez & Juan M. López-Romero

  2. Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100, Granada, Spain

    María C. Leiva, Raúl Ortiz, Gloria Perazzoli, Consolación Melguizo & Jose Prados

  3. Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071, Granada, Spain

    María C. Leiva, Consolación Melguizo & Jose Prados

  4. Biosanitary Institute of Granada (IBS. GRANADA), SAS-Universidad de Granada, 18014, Granada, Spain

    María C. Leiva, Consolación Melguizo & Jose Prados

  5. Department of Health Science, University of Jaén, 23071, Jaén, Spain

    Raúl Ortiz

  6. Department of Pharmacology, Institute of Neuroscience, Biomedical Research Center (CIBM), University of Granada, 18100, Granada, Spain

    Jose M. Baeyens

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  1. Rafael Contreras-Cáceres
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Correspondence to Consolación Melguizo.

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Contreras-Cáceres, R., Leiva, M.C., Ortiz, R. et al. Paclitaxel-loaded hollow-poly(4-vinylpyridine) nanoparticles enhance drug chemotherapeutic efficacy in lung and breast cancer cell lines. Nano Res. 10, 856–875 (2017). https://doi.org/10.1007/s12274-016-1340-2

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