Quantitative drug release monitoring in tumors of living subjects by magnetic particle imaging nanocomposite.
Quantitative drug release monitoring in tumors of living subjects by magnetic particle imaging nanocomposite.
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DOI：
10.1021/acs.nanolett.9b01202
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发表时间：
2019-09
期刊：
影响因子：
10.8
通讯作者：
Xingjun Zhu;Jian-feng Li;Peng Peng-Peng;Niloufar Hosseini Nassab;B. Smith
中科院分区：
文献类型：
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作者：
Xingjun Zhu;Jian-feng Li;Peng Peng-Peng;Niloufar Hosseini Nassab;B. Smith
体内药物释放监测为指导给药提供准确可靠的信息。基于图像的体内监测策略是有利的，因为它们是非侵入性的，并提供药物空间分布的可视化，但那些正在使用的成像方式（如荧光成像（FI）和磁共振成像（MRI））仍然不足，因为低组织渗透深度（FI）或难以量化释放率和与噪声源的信号卷积。磁颗粒成像（MPI）采用超顺磁性纳米颗粒作为造影剂和唯一信号源，可实现大组织穿透和可量化的信号强度。这些特性使其非常适合用于体内药物释放监测。在这项工作中，我们设计了一种超顺磁性Fe3O4 nanocluster@poly（乳酸-羟基乙醇酸）（PLGA）核壳纳米复合材料，负载化疗药物（阿霉素），作为双重药物递送系统和MPI定量示踪剂。制备的纳米复合材料在pH=6.5的弱酸性微环境下可降解，诱导阿霉素的持续释放和Fe3O4纳米团簇的逐渐分解，导致MPI信号发生变化。结果表明，纳米复合材料诱导的MPI信号变化与阿霉素释放率随时间呈线性相关（R2=0.99）。利用这一现象，我们成功地建立了细胞培养中释放过程的定量监测。然后，我们在癌症治疗环境中使用小鼠乳腺癌模型进行体内药物释放监测，通过注射纳米复合材料，监测药物释放，并评估诱导的肿瘤细胞杀伤。与其他可用的监测策略相比，本研究为体内药物释放监测提供了一种改进的解决方案。这种使用生物相容性聚合物涂层氧化铁纳米复合材料的转化策略将在未来的临床应用中具有前景。
In vivo drug release monitoring provides accurate and reliable information to guide drug dosing. Image-based strategies for in vivo monitoring are advantageous because they are non-invasive and provide visualization of the spatial distribution of drug, but those imaging modalities in use (e.g. fluorescence imaging (FI) and magnetic resonance imaging (MRI)) remain inadequate because of the low tissue penetration depth (for FI) or difficulty with quantification of release rate and signal convolution with noise sources. Magnetic particle imaging (MPI), employing superparamagnetic nanoparticles as the contrast agent and sole signal source, enables large tissue penetration and quantifiable signal intensity. These properties make it ideal for application to in vivo drug release monitoring. In this work, we design a superparamagnetic Fe3O4 nanocluster@poly(lactide-co-glycolide acid) (PLGA) core-shell nanocomposite loaded with a chemotherapy drug (Doxorubicin) which serves as a dual drug delivery system and MPI quantification tracer. The as-prepared nanocomposite can degrade under a mild acidic microenvironment (pH=6.5), which induces a sustained release of Doxorubicin and gradual decomposition of the Fe3O4 nanocluster, causing the MPI signal changes. We showed that nanocomposite-induced MPI signal changes display a linear correlation with the release rate of Doxorubicin over time (R2=0.99). Utilizing this phenomenon, we successfully established quantitative monitoring of the release process in cell culture. We then performed in vivo drug release monitoring in a cancer therapy setting using a murine breast cancer model by injecting the nanocomposite, monitoring the drug release, and assessing the induced tumor cell kill. This study provides an improved solution for in vivo drug release monitoring compared to other available monitoring strategies. This translational strategy using a biocompatible polymer-coated iron oxide nanocomposite will be promising in future clinical use.