In vivo assessment of bone marrow toxicity by gold nanoparticle-based bioconjugates in Crl:CD1(ICR) mice.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Animal Facility.
Cristian
C
Berce
Department of Surgery.
Ciprian
C
Lucan
Research Center for Functional Genomics and Translational Medicine; Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy.
Bobe
B
Petrushev
Nanobiophotonics and Laser Microscopy Center, Interdisciplinary Research in Bio-Nano-Sciences - Faculty of Physics, Babes-Bolyai University.
Sanda
S
Boca
Institute for Research in Analytical Instruments.
Mirela
M
Miclean
Department of Pathophysiology, University of Veterinary Medicine.
Orsolya
O
Sarpataki
Nanobiophotonics and Laser Microscopy Center, Interdisciplinary Research in Bio-Nano-Sciences - Faculty of Physics, Babes-Bolyai University.
Simion
S
Astilean
Department of Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy.
Anca
A
Buzoianu
Research Center for Functional Genomics and Translational Medicine; Department of Hematology, Ion Chiricuta Oncology Institute.
Ciprian
C
Tomuleasa
Department of Hematology, Ion Chiricuta Oncology Institute; Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
Anca
A
Bojan
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D007275:Injections, Intravenous; D008297:Male; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D010316:Particle Size; D013249:Sternum / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
D006046:Gold
GNPs; Tween® 20; in vivo toxicology