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

Leopoldo Sitia, Katia Paolella, Michela Romano, Martina Bruna Violatto, Raffaele Ferrari, Stefano Fumagalli, Laura Colombo, Ezia Bello, Maria Grazia De Simoni, Maurizio D'Incalci, Massimo Morbidelli, Eugenio Erba, Mario Salmona, Davide Moscatelli, Paolo Bigini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number2481
JournalJournal of Nanoparticle Research
Volume16
Issue number7
DOIs
Publication statusPublished - 2014

Keywords

  • Imaging
  • Integrated platform
  • Nanomedicine
  • Nanoparticle characterization
  • Polymeric nanoparticles
  • Theranostics

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Condensed Matter Physics
  • Modelling and Simulation
  • Chemistry(all)
  • Materials Science(all)
  • Bioengineering

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