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Superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid presenting cell uptake mediated by endocytosis

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Abstract

The encapsulation of superparamagnetic nanoparticles (MNPs) in polymeric nanoparticles (NPs) with modified surfaces can improve targeted delivery and induce cell death by hyperthermia. The goals of this study were to synthesize and characterize surface modified superparamagnetic poly(methyl methacrylate) with folic acid (FA) prepared by miniemulsion polymerization (MNPsPMMA-FA) and to evaluate their in vitro cytotoxicity and cellular uptake in non-tumor cells, murine fibroblast (L929) cells and tumor cells that overexpressed folate receptor (FR) β, and chronic myeloid leukemia cells in blast crisis (K562). Lastly, hemolysis assays were performed on human red blood cells. MNPsPMMA-FA presented an average mean diameter of 135 nm and a saturation magnetization (Ms) value of 37 emu/g of iron oxide, as well as superparamagnetic behavior. The MNPsPMMA-FA did not present cytotoxicity in L929 and K562 cells. Cellular uptake assays showed a higher uptake of MNPsPMMA-FA than MNPsPMMA in K562 cells when incubated at 37 °C. On the other hand, MNPsPMMA-FA showed a low uptake when endocytosis mechanisms were blocked at low temperature (4 °C), suggesting that the MNPsPMMA-FA uptake was mediated by endocytosis. High concentrations of MNPsPMMA-FA showed hemocompatibility when incubated for 24 h in human red blood cells. Therefore, our results suggest that these carrier systems can be an excellent alternative in targeted drug delivery via FR.

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Acknowledgments

We acknowledge Laboratório Central de Microscopia Eletrônica da UFSC (LCME-UFSC) and Laboratório Multiusuário de Caracterização Magnética de Materiais (LMCMM-UFSC) for TEM images and magnetization measurements. We are also grateful to Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior, CAPES, and Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, for their financial support.

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Authors and Affiliations

  1. Department of Chemical Engineering and Food Engineering, Federal University of Santa Catarina, Florianopolis, Brazil

    Paulo Emilio Feuser, Claudia Sayer & Pedro H. Hermes de Araújo

  2. Department of Clinical Analyses, Federal University of Santa Catarina, Florianopolis, Brazil

    Amanda Virtuoso Jacques & Maria Claudia dos Santos-Silva

  3. Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Brazil

    Juan Marcelo Carpio Arévalo & Maria Eliane Merlin Rocha

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  1. Paulo Emilio Feuser
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Correspondence to Pedro H. Hermes de Araújo.

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Feuser, P.E., Jacques, A.V., Arévalo, J.M.C. et al. Superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid presenting cell uptake mediated by endocytosis. J Nanopart Res 18, 104 (2016). https://doi.org/10.1007/s11051-016-3406-1

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