A higher aspect ratio enhanced bioaccumulation and altered immune responses due to intravenously-injected aluminum oxide nanoparticles

Abstract

Aluminum oxide nanoparticles (AlO NP) have been widely utilized in a variety of areas, including in the optical, biomedical and electronic fields and in the overall development of nanotechnologies. However, their toxicological profiles are still not fully developed. This study compared the distribution and immunotoxicity of two rod-types of AlO NP. As reported previously, the two types of AlO NP had different aspect ratios (long-type: 6.2 ± 0.6, short-type: 2.1 ± 0.4), but the size and surface charge were very similar. On Day 14 after a single intravenous (IV) injection (1.25 or 5 mg/kg), both AlO NP accumulated primarily in the liver and spleen and altered the levels of redox response-related elements. The accumulated level was higher in mice exposed to the long-type AlO NP compared to the short-type. Additionally, it was noted that the levels of IL-1β, IL-8 and MCP-1 were enhanced in the blood of mice exposed to both types of AlO NP and the percentages of neutrophils and monocytes among all white blood cells were increased only in mice injected with the long-type AlO NP (5 mg/kg). In addition, as compared to the control, co-expression of CD80 and CD86 (necessary for antigen presentation) on splenocytes together with a decreased expression of chemotaxis-related marker (CD195) was attenuated by exposure to the AlO NP, especially the long-type. Taken together, the data suggest that accumulation following a single IV injection with rod-types of AlO NP is strengthened by a high aspect ratio and, subsequently, this accumulation has the potential to influence immune functions in an exposed host.

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.…”

“…S‐AlONPs were well dispersed (Figure A), whereas L‐AlONPs showed an aggregated appearance (Figure B). S‐ and L‐AlONPs had anisotropic shapes with different aspect ratios (length‐to‐diameter) of 2.1 ± 0.4, and 6.2 ± 0.6, respectively (Park, Lee, et al, ; Park, Kim, et al, ). The XRD patterns obtained from both S‐ and L‐AlONPs were primarily indexed to δ phase, although S‐AlONPs were δ phase with the I space group (PDF no.…”

“…S‐ and L‐AlONPs and AlCeONPs were purchased from Sigma‐Aldrich (catalog nos 718475, 544833 and 637866; St. Louis, MO, USA) and loaded in deionized water at a concentration of 1 mg ml −1 . As described previously (Park, Lee, et al, ; Park, Sim, et al, ; Park, Kim, et al, ), each sample was dispersed in a stable fashion by sonication twice for 10 minutes in a bath‐type sonicator (150 W, 40 kHz). The temperature of the sonicator was maintained below 30°C to prevent agglomeration between the particles.…”

“…Considering that the side‐scattered light (SSC) and forward scatter axes in the fluorescence‐activated cell sorter (FACS) system indicate cellular complexity (cellular uptake of NPs) and cell size, respectively, we performed FACS analysis using four types of cells derived from the target organ for accumulation of Al‐NPs. The spleen was kindly provided by Prof. S. Yang (Ajou University, Seoul, Korea), and splenocytes were obtained through a previously described procedure (Park, Kim, et al, ). Additionally, H9C2 cells (rat cardiomyocytes), HEK‐293 cells (human embryonic kidney cells) and RAW264.7 cells (murine peritoneal macrophage cells) were purchased from the Korean Cell Line Bank (Seoul, Korea).…”

“…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, ).…”