Biodistribution and toxicity of spherical aluminum oxide nanoparticles

Abstract

With the rapid development of the nano-industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ-aluminum oxide hydroxide nanoparticles (γ-AlOHNPs), γ-and α-AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ-AlONPs, followed by the α-AlONPs and γ-AlOHNPs. In mice, γ-AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)-8 were observed in the blood of mice dosed with γ-AlOHNPs (10 mg kg À1 ). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS-2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK-293 (kidney). The results showed γ-AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ-AlOHNPs, but not γ-AlONPs or α-AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ-AlOHNPs compared with γ-AlONPs and α-AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs.

Tissue distribution following 28 day repeated oral administration of aluminum‐based nanoparticles with different properties and the in vitro toxicity

“…Similarly, aluminum‐induced brain damage altered the level of antioxidant elements in the brain (Solfrizzi et al, ; Tripathi et al, ), and pulmonary exposure to AlONPs induced the inflammatory response with oxidative stress (Lu et al, ). Additionally, in our previous studies, AlONPs influenced the tissue homeostasis of redox reaction‐related trace elements, including Mn, Zn, Cu and Fe (Park, Sim, et al, ; Park, Kim, et al, ; Park, Lee, et al, ). In the present study, we also found that the level of redox‐reaction‐related trace elements in tissues was altered after exposure to the three types of AlONPs.…”

“…However, it is well known that the properties of NPs are rapidly altered in biological fluids, thus NPs can induce different toxicity with that expected in the manufactured condition within the biological system (Higashisaka, Nagano, Yoshioka, & Tsutsumi, ; Nel et al, ). For example, in our previous study, the accumulation and toxicity of spherical AlONPs were more marked in mice exposed to γ‐aluminum oxide hydroxide NPs compared with those of γ‐AlONPs and α‐AlONPs due to their low stability within biological systems (Park, Lee, et al, ), and the surface coating of Zn oxide NPs with phosphate and sulfide, which have very low solubility in water, did not attenuate tissue distribution and toxicity of Zn oxide NPs following 28 days of oral administration due to the higher particlization rate of Zn oxide NPs in the intestine (Park, Jeong, Yoon, & Kim, ). Additionally, the inflammatory response produced in cells exposed to AlONPs (50 and 80 nm) depended on the surface area dose instilled, but not the mass dose instilled, emphasizing the importance of media‐ and temperature‐dependent particle agglomeration levels in assessing the biological safety of nanomaterials (Duffin, Tran, Brown, Stone, & Donaldson, ).…”

“…However, knowledge regarding the relationship between the properties of AlONPs and their biodistribution is extremely limited. In our previous study, we suggested that the accumulation and toxicity of rod‐type AlONPs depend on the aspect ratio and surface area (Park, Lee, et al, ; Park, Kim, et al, ), and that the distribution and toxicity of spherical AlONPs are raised by the presence of the hydroxyl group due to their low stability within biological systems (Park, Lee, et al, ). Moreover, when exposed to macrophages, oxide‐coated Al‐NPs (50, 80 and 120 nm) induced greater toxicity and more clearly decreased phagocytic ability compared to AlONPs (30 and 40 nm) (Wagner et al, ).…”

An Overview of Nanotoxicology

“…AlONPs are less toxic than other metal-based nanomaterials. However, AlONPs have been demonstrated to induce cell death by impairing cellular components, both in-vivo and in-vitro [11]. In a study of Park et al, three different types of AlONPs, α-AlONPs and γ-AlONPs, and aluminum oxide hydroxide nanoparticles (γ-AlOHNPs) were synthesized and their distribution and biological responses in vivo (5 and 10 mg.kg -1 ) were compared.…”

“…The results demonstrated that γ-AlOHNPs caused the highest toxicity. Thus, the presence of hydroxyl groups is an important factor in determining the toxicity of AlONPs [11]. In a study of Prakash et al, AlONPs which were synthesized using microemulsion hindered the growth and multiplication of the tested bacteria, including highly multiresistant bacteria (Klebsiella Pneumonia, Salmonella typhi, and Vibrio cholera).…”