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. 2021 Dec 16;9(12):355.
doi: 10.3390/toxics9120355.

The Research of Toxicity and Sensitization Potential of PEGylated Silver and Gold Nanomaterials

Dong-Han Lee  1 , Seo-Yoon Choi  1 , Ki-Kyung Jung  1 , Jun-Young Yang  1 , Ja-Young Jeong  1 , Jae-Ho Oh  1 , Sung-Hyun Kim  1 , Jin-Hee Lee  1
Affiliations

The Research of Toxicity and Sensitization Potential of PEGylated Silver and Gold Nanomaterials

Dong-Han Lee et al. Toxics. .

Abstract

Polyethylene glycol (PEG) is a polymer used for surface modification of important substances in the modern pharmaceutical industry and biopharmaceutical fields. Despite the many benefits of PEGylation, there is also the possibility that the application and exposure of the substance may cause adverse effects in the body, such as an immune response. Therefore, we aimed to evaluate the sensitization responses that could be induced through the intercomparison of nanomaterials of the PEG-coated group with the original group. We selected gold/silver nanomaterials (NMs) for original group and PEGylated silver/gold NMs in this study. First, we measured the physicochemical properties of the four NMs, such as size and zeta potential under various conditions. Additionally, we performed the test of the NM's sensitization potential using the KeratinoSens™ assay for in vitro test method and the LLNA: 5-bromo-2-deoxyuridine (BrdU)-FCM for in vivo test method. The results showed that PEGylated-NMs did not lead to skin sensitization according to OECD TG 442 (alternative test for skin sensitization). In addition, gold nanomaterial showed that cytotoxicity of PEGylated-AuNMs was lower than AuNMs. These results suggest the possibility that PEG coating does not induce an immune response in the skin tissue and can lower the cytotoxicity of nanomaterials.

Keywords: PEGylation; alternative test; immunogenicity; nanomaterials; polyethylene glycol; skin sensitization.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
Induction of luciferase activity (orange line) and cell viability (black line) of the KeratinoSens™ assay. The cells were treated with the (A) silver nanomaterials (AgNMs), (B) gold nanomaterials (AuNMs), and PEGylated nanomaterials for (C) AgNMs, and (D) AuNMs. Data are expressed as the mean ± SEM (n = 6).
Figure 2
Figure 2
Luciferase activity (orange line) and cell viability (black line) of positive control (trans-cinnamic aldehyde, CASRN. 14371-10-9) in KeratinoSens™ assay. Data are expressed as the mean ± SEM (n = 6). The positive control was tested in parallel (concentration: 4–64 µM).3.2. Bronchoalveolar lavage fluid analysis.
Figure 3
Figure 3
Results of AgNMs skin sensitization potential in LLNA: BrdU-FCM. The assessment parameters were as follows: (A) Body weight (g), (B) Ear thickness (mm), (C) Ear weight (mg), (D) Lymph node weight (mg), (E) Lymph node cell (LNC) count (×107 cells), and (F) Stimulation Index (SI). Data are expressed as the mean ± SEM (n = 4). Each treatment group was compared with the vehicle control group to determine the statistical significance. * p < 0.05, ** p < 0.01, and *** p <0.001.
Figure 4
Figure 4
Results of PEG-AgNMs skin sensitization potential in LLNA: BrdU-FCM. The assessment parameters were as follows: (A) Body weight (g), (B) Ear thickness (mm), (C) Ear weight (mg), (D) Lymph node weight (mg), (E) Lymph node cell (LNC) count (×107 cells), and (F) Stimulation Index (SI). Data are expressed as the mean ± SEM (n = 4). Each treatment group was compared with the vehicle control group to determine the statistical significance. * p < 0.05, ** p < 0.01, and *** p <0.001.
Figure 5
Figure 5
Results of AuNMs skin sensitization potential in LLNA: BrdU-FCM. The assessment parameters were as follows: (A) Body weight (g), (B) Ear thickness (mm), (C) Ear weight (mg), (D) Lymph node weight (mg), (E) Lymph node cell (LNC) count (×107 cells), and (F) Stimulation Index (SI). Data are expressed as the mean ± SEM (n = 4). Each treatment group was compared with the vehicle control group to determine the statistical significance. * p < 0.05, ** p < 0.01, and *** p <0.001.
Figure 6
Figure 6
Results of PEG-AuNMs skin sensitization potential in LLNA: BrdU-FCM. The assessment parameters were as follows: (A) Body weight (g), (B) Ear thickness (mm), (C) Ear weight (mg), (D) Lymph node weight (mg), (E) Lymph node cell (LNC) count (×107 cells), and (F) Stimulation Index (SI). Data are expressed as the mean ± SEM (n = 4). Each treatment group was compared with the vehicle control group to determine the statistical significance. * p < 0.05, ** p < 0.01, and *** p <0.001.
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