Dual-purpose magnetic micelles for MRI and gene delivery

Abstract

Gene therapy is a promising therapeutic approach for treating disease, but the efficient delivery of genes to desired locations with minimal side effects remains a challenge. In addition to gene therapy, it is also highly desirable to provide sensitive imaging information in patients for disease diagnosis, screening and post-therapy monitoring. Here, we report on the development of dual-purpose chitosan and polyethyleneimine (PEI) coated magnetic micelles (CP-mag-micelles) that can deliver nucleic acid-based therapeutic agents and also provide magnetic resonance imaging (MRI). These ‘theranostic’ CP-mag-micelles are composed of monodisperse hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) loaded into the cores of micelles that are self-assembled from a block copolymer of poly (D, L-lactide) (PLA) and monomethoxy polyethylene glycol (mPEG). For efficient loading and protection of the nucleic acids the micelles were coated with cationic polymers, such as chitosan and PEI. The morphology and size distribution of the CP-mag-micelles were characterized and their potential for use as an MRI-probe was tested using an MRI scanner. The T2 relaxivity of micelles was similar to CP-mag-micelles confirming that coating with cationic polymers did not alter magnetism. Nanoparticles coated with chitosan:PEI at a weight ratio of 5:5 showed higher transfection efficiency in HEK293, 3T3 and PC3 cells than with weight ratios of 3:7 or 7:3. CP-mag-micelles are biocompatible, can be delivered to various organs and are safe. A single injection of CP-mag-micelles carrying reporter plasmids in vivo expressed genes for at least one week. Collectively, our results demonstrate that a structural reinforcement of SPIONs loaded in the core of an mPEG-PLA micelle coated with cationic polymers provides efficient DNA delivery and enhanced MRI potential, and affords a promising candidate for theranostics in the future.

Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

“…One of the latest developments in nanomedicine are theranostic particles, which combine imaging or diagnostic and therapeutic features in a single construct 21,22 . Wang et al for example, developed magnetic micelles for gene delivery, enabling the monitoring of the delivery efficiency after administration and Kirui et al created an immunotargeted gold-coated iron oxide NP (IONP) to visualise colorectal tumours by magnetic resonance imaging followed by treatment with hyperthermia 23,24 .…”

Gd-Doped Superparamagnetic Magnetite Nanoparticles for Potential Cancer Theranostics

“…Over the last two decades, MNPs have been increasingly exploited as platforms for the transport of therapeutics including drugs and genes [46,87,88]. In magnetic drug delivery, a drug or a therapeutic reagent is conjugated to the nanoparticle and introduced in the body, and concentrated in the target area by means of a magnetic field gradient (using an internally implanted permanent magnet or an externally applied field) [89].…”

Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells

“…After 24 hours of incubation in a humidified incubator (5% CO 2 ) at 37°C, Bel-7402 cells (5×10 6 ) were mixed with folate-PEG-P(GA-DIP) nanomicelles at different iron (Fe) concentrations (0.358, 0.179, 0.0895, and 0.04475 µg/mL). After 2 hours of incubation, the cells were washed three times with 1 mL PBS, and then digested using pancreatic enzyme.…”

“…[5][6][7] However, similar to the drug's encapsulation, the high contrast parameters of SPIONs depend on the stability and loading efficiency of the micelles, which may require the specific and smart modification of the nanocarriers. During the storage and transportation of drug carriers, widely practiced core cross-linking effectively prevents the encapsulated agents from being released and the shell-core structure from decomposing prematurely.…”