Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Shenzhen Key Laboratory of Synthetic Biology, Department of Physiology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, People's Republic of China.
Key Laboratory of Optoelectronics Devices and Systems of Ministry of Education/Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, People's Republic of China.
Int J Nanomedicine. 2020 Mar 20;15:1951-1965. doi: 10.2147/IJN.S241332. eCollection 2020.
Indium phosphide (InP) quantum dots (QDs) have shown a broad application prospect in the fields of biophotonics and nanomedicine. However, the potential toxicity of InP QDs has not been systematically evaluated. In particular, the effects of different surface modifications on the biodistribution and toxicity of InP QDs are still unknown, which hinders their further developments. The present study aims to investigate the biodistribution and in vivo toxicity of InP/ZnS QDs.
Three kinds of InP/ZnS QDs with different surface modifications, hQDs (QDs-OH), aQDs (QDs-NH), and cQDs (QDs-COOH) were intravenously injected into BALB/c mice at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively. Biodistribution of three QDs was determined through cryosection fluorescence microscopy and ICP-MS analysis. The subsequent effects of InP/ZnS QDs on histopathology, hematology and blood biochemistry were evaluated at 1, 3, 7, 14 and 28 days post-injection.
These types of InP/ZnS QDs were rapidly distributed in the major organs of mice, mainly in the liver and spleen, and lasted for 28 days. No abnormal behavior, weight change or organ index were observed during the whole observation period, except that 2 mice died on Day 1 after 25 mg/kg BW hQDs treatment. The results of H&E staining showed that no obvious histopathological abnormalities were observed in the main organs (including heart, liver, spleen, lung, kidney, and brain) of all mice injected with different surface-functionalized QDs. Low concentration exposure of three QDs hardly caused obvious toxicity, while high concentration exposure of the three QDs could cause some changes in hematological parameters or biochemical parameters related to liver function or cardiac function. More attention needs to be paid on cQDs as high-dose exposure of cQDs induced death, acute inflammatory reaction and slight changes in liver function in mice.
The surface modification and exposure dose can influence the biological behavior and in vivo toxicity of QDs. The surface chemistry should be fully considered in the design of InP-based QDs for their biomedical applications.
磷化铟（InP）量子点（QDs）在生物光子学和纳米医学领域具有广泛的应用前景。然而，InP QDs 的潜在毒性尚未得到系统评估。特别是，不同表面修饰对 InP QDs 的生物分布和毒性的影响尚不清楚，这阻碍了它们的进一步发展。本研究旨在研究 InP/ZnS QDs 的生物分布和体内毒性。
三种不同表面修饰的 InP/ZnS QDs（hQDs[QDs-OH]、aQDs[QDs-NH]和 cQDs[QDs-COOH]）分别以 2.5 mg/kg BW 或 25 mg/kg BW 的剂量静脉注射到 BALB/c 小鼠体内。通过冷冻切片荧光显微镜和 ICP-MS 分析确定三种 QDs 的生物分布。随后，在注射后 1、3、7、14 和 28 天评估 InP/ZnS QDs 对组织病理学、血液学和血液生化学的影响。
这些类型的 InP/ZnS QDs 迅速分布在小鼠的主要器官中，主要在肝脏和脾脏中，并持续 28 天。在整个观察期间，除了 2 只小鼠在 25 mg/kg BW hQDs 治疗后第 1 天死亡外，没有观察到异常行为、体重变化或器官指数。H&E 染色结果表明，所有注射不同表面功能化 QDs 的小鼠的主要器官（包括心脏、肝脏、脾脏、肺、肾脏和大脑）均未观察到明显的组织病理学异常。低浓度暴露于三种 QDs 几乎不会引起明显的毒性，而三种 QDs 的高浓度暴露会引起一些与肝功能或心功能相关的血液学参数或生化参数的变化。需要更多关注 cQDs，因为高剂量暴露于 cQDs 会导致小鼠死亡、急性炎症反应和肝功能轻微变化。
表面修饰和暴露剂量会影响 QDs 的生物学行为和体内毒性。在设计基于 InP 的 QDs 用于生物医学应用时，应充分考虑表面化学。
