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10 26, 2021;15 (10): 15803-15814.

Microvilli Adhesion: An Alternative Route for Nanoparticle Cell Internalization.

Patrizia Sommi, Agostina Vitali, Stefania Coniglio, Daniele Callegari, Sofia Barbieri, Alberto Casu, Andrea Falqui, Lorenzo Vigano', Barbara Vigani, Franca Ferrari, Umberto Anselmi-Tamburini
Author Information
  1. Patrizia Sommi: Human Physiology Unit, Department of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy. ORCID
  2. Agostina Vitali: Department of Chemistry, University of Pavia, 27100 Pavia, Italy.
  3. Stefania Coniglio: Human Physiology Unit, Department of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
  4. Daniele Callegari: Department of Chemistry, University of Pavia, 27100 Pavia, Italy.
  5. Sofia Barbieri: Department of Physics, University of Pavia, 27100 Pavia, Italy.
  6. Alberto Casu: Biological and Environmental Sciences and Engineering Division, NABLA Lab, King Abdullah University of Science and Technology (KAUST), 23955-6900 Thuwal, Saudi Arabia.
  7. Andrea Falqui: Biological and Environmental Sciences and Engineering Division, NABLA Lab, King Abdullah University of Science and Technology (KAUST), 23955-6900 Thuwal, Saudi Arabia. ORCID
  8. Lorenzo Vigano': Department of Chemistry, University of Pavia, 27100 Pavia, Italy.
  9. Barbara Vigani: Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy.
  10. Franca Ferrari: Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy.
  11. Umberto Anselmi-Tamburini: Department of Chemistry, University of Pavia, 27100 Pavia, Italy. ORCID
PMID: 34585565 DOI: 10.1021/acsnano.1c03151

Abstract

The cellular uptake of nanoparticles (NPs) represents a critical step in nanomedicine and a crucial point for understanding the interaction of nanomaterials with biological systems. No specific mechanism of uptake has been identified so far, as the NPs are generally incorporated by the cells through one of the few well-known endocytotic mechanisms. Here, an alternative internalization route mediated by microvilli adhesion is demonstrated. This microvillus-mediated adhesion (MMA) has been observed using ceria and magnetite NPs with a dimension of <40 nm functionalized with polyacrylic acid but not using NPs with a neutral or positive functionalization. Such an adhesion was not cell specific, as it was demonstrated in three different cell lines. MMA was also reduced by modifications of the microvillus lipid rafts, obtained by depleting cholesterol and altering synthesis of sphingolipids. We found a direct relationship between MAA, cell cycle, and density of microvilli. The evidence suggests that MMA differs from the commonly described uptake mechanisms and might represent an interesting alternative approach for selective NP delivery.

Keywords

CeO2 HeLa adhesion/internalization cell microvilli nanoparticles

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MeSH Term

Biological Transport
Endocytosis
Microvilli
Nanomedicine
Nanoparticles
Journal Article Research Support, Non-U.S. Gov't

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