Title

Surface-Charge-Dependent Cell Localization and Cytotoxicity of Cerium Oxide Nanoparticles

Authors

Authors

A. Asati; S. Santra; C. Kaittanis;J. M. Perez

Comments

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Abbreviated Journal Title

ACS Nano

Keywords

polymer-coated nanoceria; nanoparticle cell uptake; cerium oxide; nanotoxicity; lysosomal uptake; DENDRITIC CELLS; PH; MEMBRANE; TOXICITY; CANCER; RESONANCE; EXPOSURE; THERAPY; TUMORS; MODEL; Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &; Nanotechnology; Materials Science, Multidisciplinary

Abstract

Cerium oxide nanoparticles (nanoceria) have shown great potential as antioxidant and radioprotective agents for applications in cancer therapy. Recently, various polymer-coated nanoceria preparations have been developed to improve their aqueous solubility and allow for surface functionalization of these nanoparticles. However, the interaction of polymer-coated nanoceria with cells, their uptake mechanism, and subcellular localization are poorly understood. Herein, we engineered polymer-coated cerium oxide nanoparticles with different surface charges (positive, negative, and neutral) and studied their internalization and toxicity in normal and cancer cell lines. The results showed that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g., cytoplasm and lysosomes) depending on the nanoparticle's surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticles' cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cells. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells. Taken together, these results indicate that the differential surface-charge-dependent localization of nanoceria in normal and cancer cells plays a critical role in the nanoparticles' toxicity profile.

Journal Title

Acs Nano

Volume

4

Issue/Number

9

Publication Date

1-1-2010

Document Type

Article

Language

English

First Page

5321

Last Page

5331

WOS Identifier

WOS:000282121000046

ISSN

1936-0851

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