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Arg-Gly-Asp 肽偶联的 CdSe/ZnS 量子点瘤内注射在荷胰腺癌小鼠中的生物分布和毒性评估。

Biodistribution and toxicity assessment of intratumorally injected arginine-glycine-aspartic acid peptide conjugated to CdSe/ZnS quantum dots in mice bearing pancreatic neoplasm.

机构信息

Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.

Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.

出版信息

Chem Biol Interact. 2018 Aug 1;291:103-110. doi: 10.1016/j.cbi.2018.06.014. Epub 2018 Jun 14.

DOI:10.1016/j.cbi.2018.06.014
PMID:29908985
Abstract

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 Cd 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 Cd 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.

摘要

量子点(QD)与精氨酸-甘氨酸-天冬氨酸(RGD)肽(整合素拮抗剂)缀合是具有高摩尔消光系数独特光学特性的新型纳米材料,它们具有作为光动力疗法(PDT)中的光敏剂的潜在用途。我们的小组之前已经证明了使用 QD-RGD 进行 PDT 对胰腺肿瘤细胞的显著益处。本研究旨在评估 QD-RGD 在体内应用前在小鼠体内的分布和毒性。患有胰腺肿瘤的小鼠经肿瘤内注射不同剂量的 QD-RGD,并比较注射后 0-24 小时的体内分布与对照组(静脉注射未缀合的 QD)。收集各种组织样本进行毒性分析,包括电感耦合等离子体质谱法(ICP-MS)以评估 Cd 浓度和苏木精-伊红染色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 数据显示,由于 QD 释放 Cd 而没有明显的坏死迹象。注射后 4 周内,小鼠存活良好,没有明显的虚弱或体重减轻。这些发现为 QD-RGD 的体内分布提供了新的见解,并鼓励进行深入的体内研究,而无需考虑安全性问题。这些发现缓解了安全性担忧,并为 QD-RGD 的体内分布提供了新的见解,为全面的体内研究奠定了坚实的基础。

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