Magnetite-Nanoparticle-Encapsulated pH-Responsive Polymeric Micelle as an MRI Probe for Detecting Acidic Pathologic Areas
Magnetite-Nanoparticle-Encapsulated pH-Responsive Polymeric Micelle as an MRI Probe for Detecting Acidic Pathologic Areas
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DOI：
10.1002/smll.200902317
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发表时间：
2010-06-06
期刊：
影响因子：
13.3
通讯作者：
Lee, Doo Sung
中科院分区：
文献类型：
--
作者：
Gao, Guang Hui;Im, Geun Ho;Lee, Doo Sung
纳米尺寸的颗粒越来越多地用于生物医学应用，[1]作为聚合物胶束携带疏水成像标记物和/或用于疾病诊断和治疗的药物。[2]通常，水介质中的这些聚合物胶束由疏水核和亲水冠组成，有时与可以靶向疾病生物标志物的活性靶向配体（例如，抗体、肽、核酸）缀合。[2a-c]另一方面，一些单独的聚合物胶束，不与靶向配体缀合，也可以通过刺激响应机制靶向病理组织，其中pH、温度或氧化还原可以是刺激条件。[3]在这种情况下，pH响应性聚合物胶束被用于在酸性pH环境中具有反应性，然后将其溶解在酸性pH环境中。我们设想，如果我们将经常用作磁共振成像（MRI）造影剂的磁铁矿纳米颗粒（Fe3O4）封装到pH响应性聚合物胶束中，则所得的负载Fe3O4纳米颗粒的pH响应性聚合物胶束可用作MRI的造影剂，以靶向并同时对pH刺激组织（如癌组织）进行成像。本文报道了一种pH敏感的聚合物胶束，它可以很好地包裹Fe_3O_4纳米粒子，并将其应用于酸性病理区域的诊断成像作为亲水性组分的聚乙二醇（PEG）和作为pH敏感性链段的聚（b-氨基酯）（PAE）组分（方案1）。该PEG-PAE二嵌段共聚物通过Michael型逐步聚合方法合成（参见支持信息）。[4]PAE是一种pH响应性组分，设计为在酸性环境中电离和可溶。在其主链上具有可电离叔胺基团的pH响应性PAE片段可以在低pH下接受质子以溶解或在中性或碱性pH环境下释放质子，其转化为疏水片段。[5]因此，当pH响应性PAE片段处于中性或碱性环境pH（! 7.0），它被认为是自组装聚合物胶束的疏水核心。由于PAE链段与无机纳米粒子之间的疏水相互作用，疏水的Fe3O4纳米粒子现在可以被封装到聚合物胶束的疏水核中。方案1说明了使用溶剂蒸发法制备负载Fe3O4纳米颗粒的PEG-PAE。[6]美国
Nanometer-sized particles are increasingly used for biomedical applications,[1] as polymeric micelles to carry hydrophobic imaging markers and/or drugs for disease diagnosis and therapy.[2] Usually, these polymeric micelles in an aqueous medium are composed of a hydrophobic core and a hydrophilic corona, sometimes conjugated with active-targeting ligands (eg, antibody, peptides, nucleic acids) that can target the biomarker of a disease.[2a–c] On the other hand, some polymeric micelles alone, not conjugated with a targeting ligand, can also target the pathologic tissue by a stimuli-response mechanism, with which pH, temperature, or redox can be a stimulus condition.[3] In this context, a pH-responsive polymeric micelle is utilized to be reactive in an acidic-pH environment, in which it is then dissolved. We envisioned that if we encapsulate magnetite nanoparticles (Fe3O4), which are frequently used as a contrast agent for magnetic resonance imaging (MRI), into the pH-responsive polymeric micelle, the resulting Fe3O4-nanoparticle-loaded pH-responsive polymeric micelle could be used as a contrast agent for MRI to target and, simultaneously, image the pH-stimuli tissue, such as cancerous tissue. Herein, we report a facile and powerful pH-responsive polymeric micelle that can well encapsulate Fe3O4 nanoparticles, and its potential applications in medicine for diagnostic imaging of acidic pathologic areas.The polymeric micelle, formed by a diblock copolymer in the aqueous system, contains methoxy poly (ethylene glycol)(PEG) as a hydrophilic component, and a poly (b-amino ester)(PAE) component as a pH-sensitive segment (Scheme 1). This PEG-PAE diblock copolymer was synthesized via a Michaeltype step-polymerization method(see Supporting Information).[4] The PAE is a pH-responsive component that is designed to be ionized and soluble in an acidic environment. The pH-responsive PAE segment with ionizable tertiary amine groups on its backbone can accept protons at low pH to be soluble or to release protons at neutral or basic pH environment, which is transformed into a hydrophobic segment.[5] Therefore, when the pH-responsive PAE segment is in the neutral or basic environment pH (! 7.0), it is considered to be the hydrophobic core of self-assembling polymeric micelles. The hydrophobic Fe3O4 nanoparticles can now be encapsulated into the hydrophobic core of polymeric micelles owing to the hydrophobic interaction between the PAE segment and inorganic nanoparticles. Scheme 1 illustrates the preparation of Fe3O4-nanoparticle-loaded PEG-PAE using a solventevaporation method.[6]