Original Article
Real-time liver uptake and biodistribution of magnetic nanoparticles determined by AC biosusceptometry

https://doi.org/10.1016/j.nano.2017.02.005Get rights and content

Abstract

We describe the development of a joint in vivo/ex vivo protocol to monitor magnetic nanoparticles in animal models. Alternating current biosusceptometry (ACB) enables the assessment of magnetic nanoparticle accumulation, followed by quantitative analysis of concentrations in organs of interest. We present a study of real-time liver accumulation, followed by the assessment of sequential biodistribution using the same technique. For quantification, we validated our results by comparing all of the data with electron spin resonance (ESR). The ACB had viable temporal resolution and accuracy to differentiate temporal parameters of liver accumulation, caused by vasculature extravasation and macrophages action. The biodistribution experiment showed different uptake profiles for different doses and injection protocols. Comparisons with the ESR system indicated a correlation index of 0.993. We present the ACB system as an accessible and versatile tool to monitor magnetic nanoparticles, allowing in vivo and real-time evaluations of distribution and quantitative assessments of particle concentrations.

Graphical Abstract

We describe the development of a joint in vivo/ex vivo protocol to monitor magnetic nanoparticles by AC Biosusceptometry (ACB). We present a technique to perform accumulation studies in real time, followed by biodistribution assessments with the same method. For this last step, we performed a validation study, comparing our data with Electron Spin Resonance. The ACB system showed unique temporal resolution and accuracy to assess nanoparticles accumulation in real time. The biodistribution showed different uptake profiles for doses and injection protocols. We introduce the ACB system as a versatile tool with future applications in drug delivery and cancer biology studies.

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Section snippets

AC biosusceptometry

The ACB system has been previously described35, 41 and is illustrated in Figure 1. It works as a double magnetic flux transformer with two identical pickup coil pairs that are arranged on a first-order gradiometric configuration, in which one pair (excitation/detection), farther from the sample works as a system reference. The excitation coils generate an AC magnetic field, inducing current into the detection coils at a constant rate. When no magnetic material is near the measurement probe

Dynamic liver accumulation of MNPs determined by AC biosusceptometry

Figure 3 illustrates the dynamic evaluation process. Figure 3A shows an example of the acquired ACB signal for the control and G3 groups. This signal pattern corresponded to the increasing concentrations of nanoparticles in the liver after each injection. The data from the control group showed no increase. Figure 3B shows the fitting curves for such processes, which allowed us to assess the dynamic accumulation pattern. For comparison purposes, in Figure 3C, we disregarded both the injection

Discussion

The present real-time in vivo study investigated the liver accumulation of SPIONs and changes in this parameter that were caused by different administration protocols. We applied the same technique to quantitatively assess the way in which these changes influenced biodistribution patterns. All of the quantitative data were compared with a gold standard technique (ESR), which indicated the reliability of our method.

Although many studies have reported the uptake process as a multi-compartment

Conclusion

In this study, we performed a non-invasive, dynamic evaluation on MNP accumulation with direct relation to biodistribution assessment. Our results showed that sequential injections induce different accumulation rate, although these modifications did not change significantly the biodistribution profile. This result was confirmed by the ex vivo biodistribution study, which showed that, under physiological conditions, the administration protocol will not change the final destination of

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    Funding: This work was supported by the Sao Paulo Research Foundation (FAPESP; grant no. 2010/07639–9, 2011/18696–6, 2013/20842–6, and 2015/14914–0).

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