Variations in Biodistribution and Acute Response of Differently Shaped Titania Nanoparticles in Healthy Rodents

Author:

Violatto Martina B.1,Sitia Giovanni2ORCID,Talamini Laura1,Morelli Annalisa1ORCID,Tran Ngoc Lan2,Zhang Qian3ORCID,Masood Atif4,Pelaz Beatriz5,Chakraborty Indranath6ORCID,Cui Daxiang3,Parak Wolfgang J.7ORCID,Salmona Mario1ORCID,Bastús Neus G.89ORCID,Puntes Victor891011,Bigini Paolo1

Affiliation:

1. Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy

2. Experimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy

3. Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China

4. Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN), 75530 Karachi, Pakistan

5. Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Inorgánica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain

6. School of Nano Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India

7. Center for Hybrid Nanostructures (CHyN), Universität Hamburg, Luruper Chaussee 149, 22607 Hamburg, Germany

8. Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain

9. Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain

10. Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas CSIC and the Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, 08036 Barcelona, Spain

11. CIBER en Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, 28029 Madrid, Spain

Abstract

Titanium dioxide nanoparticles (TiO2 NPs) are one of the main sources of the nanoparticulate matter exposure to humans. Although several studies have demonstrated their potential toxic effects, the real nature of the correlation between NP properties and their interaction with biological targets is still far from being fully elucidated. Here, engineered TiO2 NPs with various geometries (bipyramids, plates, and rods) have been prepared, characterized and intravenously administered in healthy mice. Parameters such as biodistribution, accumulation, and toxicity have been assessed in the lungs and liver. Our data show that the organ accumulation of TiO2 NPs, measured by ICP-MS, is quite low, and this is only partially and transiently affected by the NP geometries. The long-lasting permanence is exclusively restricted to the lungs. Here, bipyramids and plates show a higher accumulation, and interestingly, rod-shaped NPs are the most toxic, leading to histopathological pulmonary alterations. In addition, they are also able to induce a transient increase in serum markers related to hepatocellular injury. These results indicate that rods, more than bipyramidal and spherical geometries, lead to a stronger and more severe biological effect. Overall, small physico-chemical differences can dramatically modify both accumulation and safety.

Funder

National Key Research and Development Program of China

Projects of International Cooperation and Exchanges NSFC

National Natural Science Foundation of China

MCIN/AEI

Deutsche Forschungsgemeinschaft

Italian Association for Cancer Research

Spanish Ministerio de Ciencia, Innovación y Universidades

CONCORD project

Publisher

MDPI AG

Subject

General Materials Science,General Chemical Engineering

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