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An integrated approach for the systematic evaluation of polymeric nanoparticles in healthy and diseased organisms

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Abstract

Innovative strategies that utilize nanoparticles (NPs) for a better delivery of drugs and to improve their therapeutic efficacy have been widely studied in many clinical fields, including oncology. To develop safe and reliable devices able to reach their therapeutic target, a hierarchical characterization of NP interactions with biological fluids, cells, and whole organisms is fundamental. Unfortunately, this aspect is often neglected and the development of standardized characterization methods would be of fundamental help to better elucidate the potentials of nanomaterials, even before the loading of the drugs. Here, we propose a multimodal in vitro/in vivo/ex vivo platform aimed at evaluating these interactions for the selection of the most promising NPs among a wide series of materials. To set the system, we used non-degradable fluorescent poly(methyl-methacrylate) NPs of different sizes (50, 100, and 200 nm) and surface charges (positive and negative). First we studied NP stability in biological fluids. Then, we evaluated NP interaction with two cell lines of triple-negative breast cancer (TNBC), 4T1, and MDA-MB231.1833, respectively. We found that NPs internalize in TNBC cells depending on their physico-chemical properties without toxic effects. Finally, we studied NP biodistribution in terms of tissue migration and progressive clearance in breast-cancer bearing mice. The use of highly stable poly(methyl-methacrylate) NPs enabled us to track them for a long time in cells and animals. The application of this platform to other nanomaterials could provide innovative suggestions for the development of a systematic method of characterization to select the most reliable nanodrug candidates for biomedical applications.

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Acknowledgments

The authors are grateful to Mr. Ciprian Husanu and Dr. Rupert Ecker from TissueGnostics for technical help in quantification of fluorescent signals. A particular thanks to Dr. Laura Confalonieri, Dr. Stefano Pezzati, and Dr. Annamaria Mauro from Hamamatsu Photonics Italia for the support in acquiring images. L.S. is indebted to a private donor who is funding his research. The authors are grateful to AIRC for support for this research with the Special Program Molecular Clinical Oncology “5 per mille.”

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Authors and Affiliations

  1. IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156, Milan, Italy

    Leopoldo Sitia, Katia Paolella, Michela Romano, Martina Bruna Violatto, Stefano Fumagalli, Laura Colombo, Ezia Bello, Maria Grazia De Simoni, Maurizio D’Incalci, Eugenio Erba, Mario Salmona & Paolo Bigini

  2. Department of Chemistry, Materials and Chemical Engineering ‘Giulio Natta’, Politecnico di Milano, Via Luigi Mancinelli 7, 20131, Milan, Italy

    Raffaele Ferrari, Massimo Morbidelli & Davide Moscatelli

  3. Neurosurgical Intensive Care Unit, Fondazione IRCCS Ca’ Granda/Ospedale Maggiore Policlinico, Via Francesco Sforza, 33, 20122, Milan, Italy

    Stefano Fumagalli

  4. Institute for Chemical and Bioengineering, ETH Zurich, 8093, Zurich, Switzerland

    Massimo Morbidelli

Authors
  1. Leopoldo Sitia
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  2. Katia Paolella
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  3. Michela Romano
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  9. Maria Grazia De Simoni
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Corresponding author

Correspondence to Paolo Bigini.

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Sitia, L., Paolella, K., Romano, M. et al. An integrated approach for the systematic evaluation of polymeric nanoparticles in healthy and diseased organisms. J Nanopart Res 16, 2481 (2014). https://doi.org/10.1007/s11051-014-2481-4

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  • DOI: https://doi.org/10.1007/s11051-014-2481-4

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