Towards ideal magnetofluorescent nanoparticles for bimodal detection of breast-cancer cells

Fabio Corsi, Clara De Palma, Miriam Colombo, Raffaele Allevi, Manuela Nebuloni, Silvia Ronchi, Giuseppina Rizzi, Antonella Tosoni, Emilio Trabucchi, Emilio Clementi, Davide Prosperi

Research output: Contribution to journalArticlepeer-review

Abstract

An increasing number of novel molecular markers based on nanomaterials for tumor diagnostics have been developed in recent years. Many efforts have focused on the achievement of site-targeted bioconjugated nanoparticles. In contrast, the mechanisms of toxicity, endocytosis, and degradation pathways are still poorly understood, despite their primary importance for clinical translation. In this study, three different model nanoscale magnetofluorescent par icle sys ems (MFNs) are designed and fabrica ed. These nanopar icles are evaluated in terms of size, morphology, zeta potential, fluorescence efficiency, capability of enhancing T2 relaxivity of water protons, and stability. Accordingly, two are developed and the mechanism of internalization, the intracellular fate, and the toxicity in MCF-7 adenocarcinoma cells are studied. Besides the well-documented size effect, the anionic charge seems to be a crucial factor for particle internalization, as MFN penetration through the cell membrane could be modulated by surface charge. Ultrastructural analysis of transmission electron micrographs combined with evidence from confocal microscopy reveals that MFNs are internalized by clathrin-mediated endocytosis and macropinocytosis. Moreover, MFNs are found in EEA1-positive endosomes and in lysosomes, indicating that they follow a physiological pathway of endocytosis. Magnetorelaxometric analysis demonstrates that MFNs enable the detection of 5 × 105 cells mL-1 after treatment with particle dosages as low as 30 μg mL-1. Hence, MFNs appear to be a valuable and safe bimodal contrast agent that can be developed for the noninvasive diagnosis of breast cancer.

Original languageEnglish
Pages (from-to)2555-2564
Number of pages10
JournalSmall
Volume5
Issue number22
DOIs
Publication statusPublished - Nov 16 2009

Keywords

  • Cells
  • Magnetic materials
  • Nanoparticles
  • Toxicity
  • Tumor diagnostics

ASJC Scopus subject areas

  • Biomaterials
  • Engineering (miscellaneous)
  • Biotechnology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Towards ideal magnetofluorescent nanoparticles for bimodal detection of breast-cancer cells'. Together they form a unique fingerprint.

Cite this