International Journal of Nanomedicine (Sep 2016)
In vivo assessment of bone marrow toxicity by gold nanoparticle-based bioconjugates in Crl:CD1(ICR) mice
Abstract
Cristian Berce,1,* Ciprian Lucan,2,* Bobe Petrushev,3,4 Sanda Boca,5 Mirela Miclean,6 Orsolya Sarpataki,7 Simion Astilean,5 Anca Buzoianu,8 Ciprian Tomuleasa,3,9 Anca Bojan9,10 1Animal Facility, 2Department of Surgery, 3Research Center for Functional Genomics and Translational Medicine, 4Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy, 5Nanobiophotonics and Laser Microscopy Center, Interdisciplinary Research in Bio-Nano-Sciences – Faculty of Physics, Babes-Bolyai University, 6Institute for Research in Analytical Instruments, 7Department of Pathophysiology, University of Veterinary Medicine, 8Department of Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 9Department of Hematology, Ion Chiricuta Oncology Institute, 10Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania *These authors contributed equally to this work Introduction: The present study aimed at evaluating the biodistribution of Tween® 20-gold nanoparticle (GNP) conjugates and their potential toxicity on the bone marrow before moving on to Phase I clinical trials.Materials and methods: Tween® 20-conjugated GNPs were injected intravenously for 21 days in male Crl:CD1(ICR) mice. Body weight of the mice was evaluated each day. After the sub-chronic Tween® 20-GNPs administration, blood samples were harvested, and a full blood count was done individually. Total Au quantity from all major organs was assessed using inductively coupled plasma mass spectrometry. One femur and the sternum obtained from each animal were used for histological assessment.Results: Our data showed that the Tween® 20-GNP conjugates were found in large quantities in the bladder. Au was shown to accumulate in the hematopoietic bone tissue, with significant side effects such as leucopoiesis and megakaryopoiesis. The mice had a higher white blood cell and platelet count as opposed to the control group. This suggested that the previously described leukopenic effects of isoflurane were overridden by the leucopoietic effects of Tween® 20-GNPs.Conclusion: It was uncertain whether the mice were reactive to Au as it is a foreign substance to the tissues or whether the side effects observed were a precursor condition of a more severe hematological condition. Au was found to be hepatotoxic, urging the need for further studies in order to achieve better in vivo compliance and exploit the immense potential of GNPs in cancer pharmacology. Keywords: GNPs, Tween® 20, in vivo toxicology
