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Biodistribution and toxicity assessment of intratumorally injected arginine–glycine–aspartic acid peptide conjugated to CdSe/ZnS quantum dots in mice bearing pancreatic neoplasm
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2018-06-14 , DOI: 10.1016/j.cbi.2018.06.014
Ming-Ming Li , Jia Cao , Jia-Chun Yang , Yu-Jie Shen , Xiao-Lei Cai , Yuan-Wen Chen , Chun-Ying Qu , Yi Zhang , Feng Shen , Min Zhou , Lei-Ming Xu

Quantum dots (QDs) conjugated with arginine–glycine–aspartic acid (RGD) peptides (which are integrin antagonists) are novel nanomaterials with the unique optical property of high molar extinction coefficient, and they have potential utility as photosensitizers in photodynamic therapy (PDT). Our group previously demonstrated significant benefits of using PDT with QD-RGD on pancreatic tumor cells. This study aimed to evaluate the biodistribution and toxicity of QD-RGD in mice prior to in vivo application. Mice with pancreatic neoplasms were intratumorally injected with varying doses of QD-RGD, and the biodistribution 0–24 h post injection was compared to that in control mice (intravenously injected with unconjugated QD). Various tissue samples were collected for toxicity analyses, which included inductively coupled plasma mass spectrometry (ICP-MS) to assess Cd2+ concentrations and hematoxylin-eosin staining for histopathological examination. Fluorescent imaging revealed relatively sufficient radiant efficiency in mice under specific conditions. The ICP-MS and HE data showed no significant signs of necrosis due to Cd2+ release by QDs. The mice survived well and had no apparent weakness or weight loss during the 4 weeks post injection. These findings provide novel insights into the biodistribution of QD-RGD and encourage profound in vivo studies regardless of safety concerns. These findings alleviate safety concerns and provide novel insights into the biodistribution of QD-RGD, offering a solid foundation for comprehensive in vivo studies.



中文翻译:

肿瘤内注射精氨酸-甘氨酸-天冬氨酸肽与CdSe / ZnS量子点结合的生物分布和毒性评估在患有胰腺肿瘤的小鼠中

与精氨酸-甘氨酸-天冬氨酸(RGD)肽(整联蛋白拮抗剂)缀合的量子点(QDs)是具有高摩尔消光系数的独特光学性质的新型纳米材料,在光动力疗法(PDT)中作为光敏剂具有潜在的用途。 。我们的研究小组先前证明了将PDT与QD-RGD一起用于胰腺肿瘤细胞具有明显的益处。这项研究旨在评估体内QD-RGD在小鼠体内的生物分布和毒性应用。向胰腺癌小鼠瘤内注射不同剂量的QD-RGD,并将注射后0-24小时的生物分布与对照组小鼠(静脉内注射未结合的QD)进行比较。收集各种组织样品进行毒性分析,包括电感耦合等离子体质谱(ICP-MS)评估Cd 2+浓度和苏木精-伊红染色以进行组织病理学检查。荧光成像显示在特定条件下小鼠具有相对足够的辐射效率。ICP-MS和HE数据未显示由于Cd 2+引起的明显坏死迹象由QD发布。小鼠在注射后4周内存活良好,并且没有明显的虚弱或体重减轻。这些发现为QD-RGD的生物分布提供了新颖的见解,并鼓励进行深入的体内研究,而不考虑安全性问题。这些发现减轻了对安全性的担忧,并为QD-RGD的生物分布提供了新颖的见解,为全面的体内研究奠定了坚实的基础。

更新日期:2018-06-14
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