1. Towards bio-compatible magnetic nanoparticles Immune-related effects, in-vitro internalization, and in-vivo bio-distribution of zwitterionic ferrite nanoparticles with unexpected renal clearance
- Author
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Laura Castiglioni, Diana Boraschi, Sandro Usseglio, Pooja Joshi, Rosa La Mattina, Luigi Sironi, Benjamin J Swartzwelter, Alessandro Ponti, Yang Li, Bice Chini, Marianna Leonzino, Uliano Guerrini, Paola Italiani, Anna M. Ferretti, Cinzia Cagnoli, Claudia Verderio, Sara Mondini, Carmelo Drago, and Paolo Gelosa
- Subjects
Biodistribution ,media_common.quotation_subject ,Nanoparticle ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Ferric Compounds ,Biomaterials ,Mice ,Colloid and Surface Chemistry ,In vivo ,Animals ,Tissue Distribution ,Internalization ,Magnetite Nanoparticles ,media_common ,Chemistry ,Biological activity ,Mononuclear phagocyte system ,Blood Proteins ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Drug delivery ,Magnetic nanoparticles ,Biophysics ,Nanoparticles ,Bio-distribution ,Microglia ,Zwitterionic nanoparticle ,0210 nano-technology ,Renal clearance ,mmune-related effects - Abstract
Hypothesis Iron oxide and other ferrite nanoparticles have not yet found widespread application in the medical field since the translation process faces several big hurdles. The incomplete knowledge of the interactions between nanoparticles and living organisms is an unfavorable factor. This complex subject should be made simpler by synthesizing magnetic nanoparticles with good physical (relaxivity) and chemical (colloidal stability, anti-fouling) properties and no biological activity (no immune-related effects, minimal internalization, fast clearance). Such an innocent scaffold is the main aim of the present paper. We systematically searched for it within the class of small-to-medium size ferrite nanoparticles coated by small (zwitter)ionic ligands. Once established, it can be functionalized to achieve targeting, drug delivery, etc. and the observed biological effects will be traced back to the functional molecules only, as the nanosized scaffold is innocent. Experiments We synthesized nine types of magnetic nanoparticles by systematic variation of core composition, size, coating. We investigated their physico-chemical properties and interaction with serum proteins, phagocytic microglial cells, and a human model of inflammation and studied their biodistribution and clearance in healthy mice. The nanoparticles have good magnetic properties and their surface charge is determined by the preferential adsorption of anions. All nanoparticle types can be considered as immunologically safe, an indispensable pre-requisite for medical applications in humans. All but one type display low internalization by microglial BV2 cells, a process strongly affected by the nanoparticle size. Both small (3 nm) and medium size (11 nm) zwitterionic nanoparticles are in part captured by the mononuclear phagocyte system (liver and spleen) and in part rapidly (≈1 h) excreted through the urinary system of mice. Findings The latter result questions the universality of the accepted size threshold for the renal clearance of nanoparticles (5.5 nm). We suggest that it depends on the nature of the circulating particles. Renal filterability of medium-size magnetic nanoparticles is appealing because they share with small nanoparticles the decreased accumulation-related toxicity while performing better as magnetic diagnostic/therapeutic agents thanks to their larger magnetic moment. In conclusion, many of our nanoparticle types are a bio-compatible innocent scaffold with unexpectedly favorable clearance.
- Published
- 2021
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