Development of Theranostic Cationic Liposomes Designed for Image-Guided Delivery of Nucleic Acid.

Hai Doan Do,Aude Michel,Corinne Marie,Johanne Seguin,Christine Ménager,Bich-Thuy Doan,Hélène Dhotel,Tawba Korichi,Nathalie Mignet

doi:10.3390/pharmaceutics12090854

Abstract

Cationic liposomes have been considered as potential vectors for gene delivery thanks to their ability to transfect cells with high efficiency. Recently, the combination of diagnostic agent and therapeutic agents in the same particle to form a theranostic system has been reported. Magnetic liposomes are one of these examples. Due to the magnetic nanoparticles encapsulated in the liposomes, they can act as a drug delivery system and, at the same time, a magnetic resonance imaging contrast enhancement agent or hyperthermia. In this work, nucleic acid delivery systems based on magnetic cationic liposomes (MCLs) were developed. Two different techniques, reverse phase evaporation and cosolvent sonication, were employed for liposome preparation. Both strategies produced MCLs of less than 200 nm with highly positive charge. Enhancement of their transverse and longitudinal relaxivities r2 and r1 was obtained with both kinds of magnetic liposomes compared to free magnetic nanoparticles. Moreover, these MCLs showed high capacity to form complexes and transfect CT-26 cells using the antibiotic-free pFAR4-luc plasmid. The transfection enhancement with magnetofection was also carried out in CT26 cells. These results suggested that our MCLs could be a promising candidate for image-guided gene therapy.

Highlights

In the late 1980s and early 1990s, gene therapy has revolutionized in the care of rare diseases by proposing to use a gene as a medicine [1,2,3]
Quant-iTTM PicoGreen®was purchased from Invitrogen (Carlsbad, CA, United States), the Luciferase assay system was purchased from Promega (Madison, WI, United States), the PierceTM bicinchoninic acid (BCA) Protein Assay Kit was from Thermo Fisher Scientific (Waltham, MA, United States), and Resazurin sodium salt was from Sigma-Aldrich
magnetic cationic liposomes (MCLs) have been studied for a long time for hyperthermia, drug delivery [43], or gene delivery purposes

Summary

Introduction

In the late 1980s and early 1990s, gene therapy has revolutionized in the care of rare diseases by proposing to use a gene as a medicine [1,2,3]. There has been a lot of innovation to minimize their side effects, viral vectors still present some disadvantages such as difficulty of mass production, high cost, low stability and limited size of the nucleic acid that can be delivered. To overcome these drawbacks, non-viral vectors are still being studied. Cationic liposomes are considered as potential candidates for gene delivery owing to their capacity to carry a large-size gene and be produced at a large scale at reasonable cost [8,9] They recently reached the clinic by carrying small interfering RNA (siRNA) in the case of Onpattro®(patisiran) for the treatment of Hereditary Transthyretin-mediated Amyloidosis (hATTR), which is a progressively incapacitating and often fatal genetic disorder

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