Quantitative drug release monitoring in tumors of living subjects by magnetic particle imaging nanocomposite.

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ID: 42376
2019
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Abstract
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.
Reference Key
zhu2019quantitativenano Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Zhu, Xingjun;Li, Jianfeng;Peng, Peng;Hosseini-Nassab, Niloufar;Smith, Bryan Ronain;
Journal Nano letters
Year 2019
DOI
10.1021/acs.nanolett.9b01202
URL
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