Evaluation of quantum dot cytotoxicity based on intracellular uptake
Evaluation of quantum dot cytotoxicity based on intracellular uptake
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DOI：
10.1002/smll.200600218
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发表时间：
2006-12-01
期刊：
影响因子：
13.3
通讯作者：
Drezek, Rebekah
中科院分区：
文献类型：
--
作者：
Chang, Emmanuel;Thekkek, Nadhi;Drezek, Rebekah
纳米材料的进步为研究和医学中的许多生物应用带来了有希望的候选材料。由于其小尺寸、化学组成、表面结构、溶解度和形状，其新颖的物理化学性质已越来越多地用于医学诊断、成像和药物递送。应用范围从细胞的荧光跟踪[1-3]和免疫染色测定[4]到磁共振成像。[5]鉴于其广泛应用和商业化的潜力，纳米材料在未来的生物学应用中将越来越受欢迎。[6]量子点（QD）是具有生物成像理想光学特性的纳米材料的一个例子，这使它们成为荧光染料的有用替代品。目前使用的有机荧光团容易受到化学和代谢降解的影响，并且容易被光漂白，这限制了长期的细胞跟踪。量子点提供的优势，如明亮的光致发光，窄发射，宽紫外激发，和高光稳定性，[7-9]，以帮助克服目前的光学成像限制。由于对开发用于成像和治疗应用的纳米颗粒的极大关注，人们对评估纳米材料的毒性越来越感兴趣，[10]特别是量子点。一些研究表明，纳米材料本身并不是良性的，会在细胞、亚细胞和蛋白质水平上影响生物系统。[11-15] Akerman等人证明，肝脏和脾脏中网状内皮系统的巨噬细胞可从活小鼠的循环中清除一些纳米颗粒。[16]然而，关于量子点的毒性的担忧已经浮出水面，特别是那些含镉的纳米颗粒，因此对细胞培养物和活体动物都有毒性。先前的体外标记实验已经证明，只要QD被良好地涂覆以具有生物惰性，QD标记[17]就可以在没有显著毒性的情况下发生。[1，18，19]尽管有这些结果，最近的工作已经证明了几个重要的参数，确定纳米颗粒的毒性，特别是量子点。具体而言，QD的毒性是由于其固有的化学组成、尺寸、形状和表面。[14事实上，控制细胞毒性的主要条件之一是使这些无机纳米颗粒水溶性的QD表面涂层的程度和稳定性。已经为QD开发了几种合成、储存和涂覆策略，以确保这些纳米颗粒的稳定性并使毒性最小化。[22-27] Derfus等人检查了用巯基乙酸水溶解的QD毒性的几个参数。[17]通过将量子点暴露于长时间的氧化环境，如空气或紫外光的光氧化，他们观察到由于纳米颗粒尺寸的减小，吸收和荧光光谱发生蓝移，从而从量子点中浸出Cd 2+。此外，他们证明了量子点的正确封盖和改进的表面涂层可以最大限度地减少由于空气和光氧化而产生的细胞毒性。[17]Hoshino等人证明，QD的毒性不依赖于QD本身，而是依赖于表面分子。[28]基于此，他们建议评估表面分子如何影响量子点的细胞毒性是重要的。这些研究考察了不同的表面分子如何改善量子点的生物相容性。最近，研究表明，纳米颗粒上的表面分子显著影响细胞对纳米颗粒的吸收程度。
Advances in nanomaterials have led to promising candidates for many biological applications in research and medicine. Their novel physicochemical properties, attributable to their small size, chemical composition, surface structure, solubility, and shape, have been increasingly utilized in medicine for purposes of diagnosis, imaging, and drug delivery. Applications range from the fluorescent tracking of cells [1–3] and immunostaining assays [4] to magnetic resonance imaging.[5] Given the potential for widespread application and commercialization, nanomaterials will be increasingly uti-ACHTUNGTRENNUNGlized for future biological applications.[6] Quantum dots (QDs) are an example of a nanomaterial that possesses optical properties ideal for biological imaging, which makes them a useful alternative to fluorescent dyes. The organic fluorophores currently used are vulnerable to chemical and metabolic degradation and are easily photobleached, which limits long-term cellular tracking. QDs offer advantages, such as bright photoluminescence, narrow emission, broad UV excitation, and high photostability,[7–9] to help overcome current optical-imaging limitations. Due to the tremendous focus on developing nanoparticles for imaging and therapeutic applications, there has been increasing interest in evaluating the toxicity of nanomaterials,[10] in particular, quantum dots. Some studies suggest that nanomaterials are not inherently benign and affect biological systems at the cellular, subcellular, and protein levels.[11–15] Akerman et al. demonstrated that some nanoparticulates are cleared from the circulation of live mice by the macrophages of the reticuloendothelial system in the liver and spleen.[16] Nevertheless, concerns have surfaced regarding the toxicity of QDs, in particular, those nanoparticles that are cadmium-containing and thus toxic to both cell cultures and live animals. Previous invitro labeling experiments have demonstrated that QD labeling [17] could occur without significant toxicity as long as the QDs are wellcoated to be biologically inert.[1, 18, 19] Notwithstanding these results, recent work has demonstrated several significant parameters that identify the toxicity of nanoparticles, in particular, QDs. Specifically, the toxicity of QDs is due to their inherent chemical composition, size, shape, and surface.[14, 15, 17, 20, 21] In fact, one of the primary conditions governing cytotoxicity is the degree and stability of the QD surface coating that makes these inorganic nanoparticles water-soluble. Several synthesis, storage, and coating strategies have been developed for QDs in order to ensure stability of these nanoparticles and minimize toxicity.[22–27] Derfus et al. examined several parameters of the toxicity of QDs water-solubilized with mercaptoacetic acid.[17] By exposing QDs to prolonged oxidative environments, such as air or photo-oxidation with UV light, they observed leaching of Cd2+ from QDs by a blue-shift in the absorbance and fluorescence spectra due to the decreasing size of the nanoparticle. Furthermore, they demonstrated that correct capping and improved surface coating of quantum dots can minimize cytotoxicity arising due to air and photo-oxidation.[17] Hoshino et al. demonstrated that toxicity of QDs is not dependent on the nanocrystal itself but rather on the surface molecules.[28] Based on this, they suggested that it was important to evaluate how surface molecules affect the cytotoxicity of QDs. These studies examined how different surface molecules improved the biocompatibility of QDs. More recently, studies have shown that the surface molecules on nanoparticles significantly affect the degree of nanoparticle uptake into cells by …