Visualization of the distribution of nanoparticle-formulated AZD2811 in mouse tumor model using matrix-assisted laser desorption ionization mass spectrometry imaging

Shoraku Ryu,Akinobu Hamada,Kan Yonemori,Tatsunori Shimoi,Shigehiro Yagishita,Yasuhiro Fujiwara,Kenji Tamura,Mayu Ohuchi

doi:10.1038/s41598-020-72665-5

Shoraku Ryu, Akinobu Hamada + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-72665-5

Copy DOI

Abstract

Penetration of nanoparticles into viable tumor regions is essential for an effective response. Mass spectrometry imaging (MSI) is a novel method for evaluating the intratumoral pharmacokinetics (PK) of a drug in terms of spatial distribution. The application of MSI for analysis of nanomedicine PK remains in its infancy. In this study, we evaluated the applicability of MALDI-MSI for nanoparticle-formulated drug visualization in tumors and biopsies, with an aim toward future application in clinical nanomedicine research. We established an analytic method for the free drug (AZD2811) and then applied it to visualize nanoparticle-formulated AZD2811. MSI analysis demonstrated heterogeneous intratumoral drug distribution in three xenograft tumors. The intensity of MSI signals correlated well with total drug concentration in tumors, indicating that drug distribution can be monitored quantitatively. Analysis of tumor biopsies indicated that MSI is applicable for analyzing the distribution of nanoparticle-formulated drugs in tumor biopsies, suggesting clinical applicability.

Highlights

Nanoparticle-based drug delivery systems are promising tools for enhancing drug delivery into tumors
We compared the sensitivity of AZD2811 detection using two different matrixes (α-CHCA and Dihydroxybenzoic acid (DHB)) and acids (FA and trifluoroacetic acid (TFA)) with free AZD2811 standard solution at a concentration of 500 pg/μL spotted on slide glass
The same evaluation was performed for D5-AZD2811, which was used as an internal standard (IS)

Summary

Introduction

Nanoparticle-based drug delivery systems are promising tools for enhancing drug delivery into tumors. Many intrinsic factors in tumors are known to influence EPR effects, such as the nature of the vascular system, properties of the stroma, and macrophage infiltration, among others[3]. These factors can vary with tumor size, location, type, and among patients, which can impact the delivery of different drugs in a tumor even with the same type of nanoparticle. We evaluated the applicability of MALDI-MSI to analyze nanoparticle-formulated AZD2811. The results indicate that MALDI-MSI is a suitable tool for imaging analyses of nanoparticle formulations in both preclinical and clinical applications. A comparison of local histologic features with drug distribution as analyzed by high spatial resolution MSI was attempted

Methods

Results

Conclusion