Molecular imaging of brain localization of liposomes in mice using MALDI mass spectrometry.

Annabelle Fülöp,Katrin Erich,Carsten Hopf,Denis A Sammour,Johanna Von Gerichten,Roger Sandhoff,Peter Van Hoogevest

doi:10.1038/srep33791

Abstract

Phospholipids have excellent biocompatibility and are therefore often used as main components of liposomal drug carriers. In traditional bioanalytics, the in-vivo distribution of liposomal drug carriers is assessed using radiolabeled liposomal constituents. This study presents matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) as an alternative, label-free method for ex-vivo molecular imaging of liposomal drug carriers in mouse tissue. To this end, indocyanine green as cargo and two liposomal markers, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with monodisperse polyethylene glycol (PEG36-DSPE) were incorporated into liposomal carriers and administered to mice. We used MALDI MSI of the two lipid markers in both positive and negative ion mode for visualization of liposome integrity and distribution in mouse organs. Additional MSI of hemoglobin in the same tissue slice and pixel-by-pixel computational analysis of co-occurrence of lipid markers and hemoglobin served as indicator of liposome localization either in parenchyma or in blood vessels. Our proof-of-concept study suggests that liposomal components and indocyanine green distributed into all investigated organs.

Highlights

Phospholipids have excellent biocompatibility and are often used as main components of liposomal drug carriers
Since only a single radiolabel can be monitored at any given time, radiochemical methods do not permit the evaluation of in-vivo liposome integrity or cargo retention and release
We hypothesized that MALDI MSI as a label-free method for simultaneous imaging of multiple masses may enable an innovative workflow that combines multiple MSI experiments across different mass scales in both polarities to address these questions in a single tissue slice

Summary

Introduction

Phospholipids have excellent biocompatibility and are often used as main components of liposomal drug carriers. This study presents matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) as an alternative, label-free method for ex-vivo molecular imaging of liposomal drug carriers in mouse tissue. To this end, indocyanine green as cargo and two liposomal markers, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with monodisperse polyethylene glycol (PEG36-DSPE) were incorporated into liposomal carriers and administered to mice. We present a MALDI MSI method for imaging of liposomal drug carriers in the presence of a matrix of natural endogenous phospholipids To this end, we imaged three liposomal components after in-vivo dosing of mice using MALDI mass spectrometry. The results suggest possible utility of MALDI MSI as a non-radioactive tool for formulation and drug delivery studies

Methods

Results

Conclusion