纳米颗粒价态在复杂介质中细胞的非破坏性磁弛豫介导检测和磁分离中的作用。
Role of nanoparticle valency in the nondestructive magnetic-relaxation-mediated detection and magnetic isolation of cells in complex media.
作者信息
Kaittanis Charalambos, Santra Santimukul, Perez J Manuel
机构信息
Nanoscience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, Florida 32826, USA.
出版信息
J Am Chem Soc. 2009 Sep 9;131(35):12780-91. doi: 10.1021/ja9041077.
Nanoparticle-based diagnostics typically involve the conjugation of targeting ligands to the nanoparticle to create a sensitive and specific nanosensor that can bind and detect the presence of a target, such as a bacterium, cancer cell, protein, or DNA sequence. Studies that address the effect of multivalency on the binding and detection pattern of these nanosensors, particularly on magnetic relaxation nanosensors that sense the presence of a target in a dose-dependent manner by changes in the water relaxation times (DeltaT2), are scarce. Herein, we study the effect of multivalency on the detection profile of cancer cells and bacteria in complex media, such as blood and milk. In these studies, we conjugated folic acid at two different densities (low-folate and high-folate) on polyacrylic-acid-coated iron oxide nanoparticles and studied the interaction of these magnetic nanosensors with cancer cells expressing the folate receptor. Results showed that the multivalent high-folate magnetic relaxation nanosensor performed better than its low folate counterpart, achieving single cancer cell detection in blood samples within 15 min. Similar results were also observed when a high molecular weight anti-folate antibody (MW 150 kDa) was used instead of the low molecular weight folic acid ligand (MW 441.4 kDa), although better results in terms of sensitivity, dynamic range, and speed of detection were obtained when the folate ligand was used. Studies using bacteria in milk suspensions corroborated the results observed with cancer cells. Taken together, these studies demonstrate that nanoparticle multivalency plays a key role in the interaction of the nanoparticle with the cellular target and modulate the behavior and sensitivity of the assay. Furthermore, as detection with magnetic relaxation nanosensors is a nondestructive technique, magnetic isolation and further characterization of the cancer cells is possible.
基于纳米颗粒的诊断通常涉及将靶向配体与纳米颗粒缀合，以创建一种灵敏且特异的纳米传感器，该传感器能够结合并检测靶标的存在，例如细菌、癌细胞、蛋白质或DNA序列。关于多价性对这些纳米传感器的结合和检测模式的影响的研究，尤其是对通过水弛豫时间（ΔT2）变化以剂量依赖方式感知靶标存在的磁弛豫纳米传感器的研究很少。在此，我们研究了多价性对复杂介质（如血液和牛奶）中癌细胞和细菌检测谱的影响。在这些研究中，我们将叶酸以两种不同密度（低叶酸和高叶酸）缀合在聚丙烯酸包覆的氧化铁纳米颗粒上，并研究了这些磁性纳米传感器与表达叶酸受体的癌细胞之间的相互作用。结果表明，多价的高叶酸磁弛豫纳米传感器比其低叶酸对应物表现更好，能够在15分钟内检测出血液样本中的单个癌细胞。当使用高分子量抗叶酸抗体（分子量150 kDa）代替低分子量叶酸配体（分子量441.4 kDa）时，也观察到了类似的结果，不过使用叶酸配体时在灵敏度、动态范围和检测速度方面获得了更好的结果。在牛奶悬浮液中使用细菌的研究证实了在癌细胞中观察到的结果。综上所述，这些研究表明纳米颗粒多价性在纳米颗粒与细胞靶标的相互作用中起关键作用，并调节检测方法的行为和灵敏度。此外，由于磁弛豫纳米传感器检测是一种非破坏性技术，因此有可能对癌细胞进行磁分离并进一步表征。
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