Hlaing Chi Be, Chariyakornkul Arpamas, Pilapong Chalermchai, Punvittayagul Charatda, Srichairatanakool Somdet, Wongpoomchai Rawiwan
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Center of Excellence for Molecular Imaging (CEMI), Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Nanomaterials (Basel). 2022 Mar 22;12(7):1040. doi: 10.3390/nano12071040.
Iron-tannic acid nanoparticles (Fe-TA NPs) presented MRI contrast enhancement in both liver cancer cells and preneoplastic rat livers, while also exhibiting an anti-proliferative effect via enhanced autophagic death of liver cancer cells. Hence, a toxicity assessment of Fe-TA NPs was carried out in the present study. Acute and systemic toxicity of intraperitoneal Fe-TA NPs administration was investigated via a single dose of 55 mg/kg body weight (bw). Doses were then repeated 10 times within a range of 0.22 to 5.5 mg/kg bw every 3 days in rats. Furthermore, clastogenicity was assessed by rat liver micronucleus assay. Carcinogenicity was evaluated by medium-term carcinogenicity assay using glutathione -transferase placental form positive foci as a preneoplastic marker, while three doses ranging from 0.55 to 17.5 mg/kg bw were administered 10 times weekly via intraperitoneum. Our study found that the LD value of Fe-TA NPs was greater than 55 mg/kg bw. Repeated dose administration of Fe-TA NPs over a period of 28 days and 10 weeks revealed no obvious signs of systemic toxicity, clastogenicity, and hepatocarcinogenicity. Furthermore, Fe-TA NPs did not alter liver function or serum iron status, however, increased liver iron content at certain dose in rats. Notably, antioxidant response was observed when a dose of 17.5 mg/kg bw was given to rats. Accordingly, our study found no signs of toxicity, genotoxicity, and early phase hepatocarcinogenicity of Fe-TA NPs in rats.
铁-单宁酸纳米颗粒（Fe-TA NPs）在肝癌细胞和癌前大鼠肝脏中均表现出磁共振成像（MRI）对比增强作用，同时还通过增强肝癌细胞的自噬性死亡发挥抗增殖作用。因此，本研究对Fe-TA NPs进行了毒性评估。通过腹腔注射55 mg/kg体重（bw）的单剂量来研究腹腔注射Fe-TA NPs的急性和全身毒性。然后在大鼠中每3天以0.22至5.5 mg/kg bw的剂量重复给药10次。此外，通过大鼠肝脏微核试验评估致断裂性。使用胎盘型谷胱甘肽转移酶阳性灶作为癌前标志物，通过中期致癌性试验评估致癌性，同时每周通过腹腔注射给予0.55至17.5 mg/kg bw的三种剂量，共10次。我们的研究发现Fe-TA NPs的半数致死量（LD）值大于55 mg/kg bw。在28天和10周的时间内重复给药Fe-TA NPs未发现明显的全身毒性、致断裂性和肝癌致癌性迹象。此外，Fe-TA NPs未改变肝功能或血清铁状态，然而，在大鼠中某些剂量下会增加肝脏铁含量。值得注意的是，当给大鼠注射17.5 mg/kg bw的剂量时观察到了抗氧化反应。因此，我们的研究未发现Fe-TA NPs在大鼠中存在毒性 signs、遗传毒性和早期肝癌致癌性的迹象。
