Chemical nature and structure of organic coating of quantum dots is crucial for their application in imaging diagnostics.
Chemical nature and structure of organic coating of quantum dots is crucial for their application in imaging diagnostics.
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DOI：
10.2147/ijn.s17995
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发表时间：
2011
影响因子：
8
通讯作者：
Saga T
中科院分区：
文献类型：
--
作者：
Bakalova R;Zhelev Z;Kokuryo D;Spasov L;Aoki I;Saga T
量子点最有吸引力的特性之一是它们有可能扩展体内荧光和多模态成像的机会。本研究的目的是阐明纳米颗粒的有机涂层的组成和结构是否对其在体内的应用至关重要。我们比较了涂覆有非交联的氨基官能化的聚酰胺胺（PAMAM）树枝状聚合物的量子点、封装在交联的羧基官能化的PAMAM树枝状聚合物中的量子点和二氧化硅壳的氨基官能化的量子点。一个多模态的荧光和顺磁量子点探针也被开发和分析。将探针静脉内应用于麻醉的动物中，以使用双光子激发荧光显微镜观察脑脉管系统，并使用荧光IVIS®成像（Caliper Life Sciences，Hopkinton，MA）和磁共振成像观察肿瘤。用非交联树枝状聚合物涂覆的量子点具有细胞毒性。它们在体内引起副作用，包括血管舒张，平均动脉血压和心率下降。量子点穿透血管，导致荧光成像质量下降。包封在交联树枝状聚合物中的量子点具有低细胞毒性和生物相容性。在浓度<0.3 nmol量子点/kg体重时，这些纳米颗粒不影响血压和心率，也不诱导血管舒张或血管收缩。聚乙二醇化（PEG [聚乙二醇]）是基于二氧化硅壳量子点的体内成像量子点探针开发中不可或缺的一步。非聚乙二醇化的二氧化硅壳量子点在高盐生理液体中具有低的胶体稳定性，伴随着在体内的快速聚集。二氧化硅壳量子点与PEG 1100的共轭增加了它们在循环中的稳定性和半衰期，而没有显著增加它们的尺寸。在浓度<2.5 nmol/kg体重时，这些量子点不影响主要生理变量。这是可能的可视化毛细血管，这使得这种量子点探针适合于调查的介质的血管收缩，血管舒张，和脑循环在体内完整的动物。多模态硅壳量子点允许使用磁共振成像在肿瘤组织发展的早期阶段进行可视化。目前的研究表明，量子点的有机/生物有机壳的类型和结构决定了它们的生物相容性，并且对于它们在体内成像中的应用是至关重要的，这是由于壳对以下性质的影响：胶体稳定性、在生理液体中的溶解度、基本生理参数的影响以及细胞毒性。
One of the most attractive properties of quantum dots is their potential to extend the opportunities for fluorescent and multimodal imaging in vivo. The aim of the present study was to clarify whether the composition and structure of organic coating of nanoparticles are crucial for their application in vivo. We compared quantum dots coated with non-crosslinked amino-functionalized polyamidoamine (PAMAM) dendrimers, quantum dots encapsulated in crosslinked carboxyl-functionalized PAMAM dendrimers, and silica-shelled amino-functionalized quantum dots. A multimodal fluorescent and paramagnetic quantum dot probe was also developed and analyzed. The probes were applied intravenously in anesthetized animals for visualization of brain vasculature using two-photon excited fluorescent microscopy and visualization of tumors using fluorescent IVIS® imaging (Caliper Life Sciences, Hopkinton, MA) and magnetic resonance imaging. Quantum dots coated with non-crosslinked dendrimers were cytotoxic. They induced side effects in vivo, including vasodilatation with a decrease in mean arterial blood pressure and heart rate. The quantum dots penetrated the vessels, which caused the quality of fluorescent imaging to deteriorate. Quantum dots encapsulated in crosslinked dendrimers had low cytotoxicity and were biocompatible. In concentrations <0.3 nmol quantum dots/kg bodyweight, these nanoparticles did not affect blood pressure and heart rate, and did not induce vasodilatation or vasoconstriction. PEGylation (PEG [polyethylene glycol]) was an indispensable step in development of a quantum dot probe for in vivo imaging, based on silica-shelled quantum dots. The non-PEGylated silica-shelled quantum dots possessed low colloidal stability in high-salt physiological fluids, accompanied by rapid aggregation in vivo. The conjugation of silica-shelled quantum dots with PEG1100 increased their stability and half-life in the circulation without significant enhancement of their size. In concentrations <2.5 nmol/kg bodyweight, these quantum dots did not affect the main physiological variables. It was possible to visualize capillaries, which makes this quantum dot probe appropriate for investigation of mediators of vasoconstriction, vasodilatation, and brain circulation in intact animals in vivo. The multimodal silica-shelled quantum dots allowed visualization of tumor tissue in an early stage of its development, using magnetic resonance imaging. The present study shows that the type and structure of organic/bioorganic shells of quantum dots determine their biocompatibility and are crucial for their application in imaging in vivo, due to the effects of the shell on the following properties: colloidal stability, solubility in physiological fluids, influence of the basic physiological parameters, and cytotoxicity.