Chondroitin sulfate-polyethylenimine copolymer-coated superparamagnetic iron oxide nanoparticles as an efficient magneto-gene carrier for microRNA-encoding plasmid DNA delivery

Abstract

MicroRNA-128 (miR-128) is an attractive therapeutic molecule with powerful glioblastoma regulation properties. However, miR-128 lacks biological stability and leads to poor delivery efficacy in clinical applications. In our previous study, we demonstrated two effective transgene carriers, including polyethylenimine (PEI)-decorated superparamagnetic iron oxide nanoparticles (SPIONs) as well as chemically-conjugated chondroitin sulfate-PEI copolymers (CPs). In this contribution, we report optimized conditions for coating CPs onto the surfaces of SPIONs, forming CPIOs, for magneto-gene delivery systems. The optimized weight ratio of the CPs and SPIONs is 2 : 1, which resulted in the formation of a stable particle as a good transgene carrier. The hydrodynamic diameter of the CPIOs is ∼136 nm. The gel electrophoresis results demonstrate that the weight ratio of CPIO/DNA required to completely encapsulate pDNA is ≥3. The in vitro tests of CPIO/DNA were done in 293 T, CRL5802, and U87-MG cells in the presence and absence of an external magnetic field. The magnetofection efficiency of CPIO/DNA was measured in the three cell lines with or without fetal bovine serum (FBS). CPIO/DNA exhibited remarkably improved gene expression in the presence of the magnetic field and 10% FBS as compared with a gold non-viral standard, PEI/DNA, and a commercial magnetofection reagent, PolyMag/DNA. In addition, CPIO/DNA showed less cytotoxicity than PEI/DNA and PolyMag/DNA against the three cell lines. The transfection efficiency of the magnetoplex improved significantly with an assisted magnetic field. In miR-128 delivery, a microRNA plate array and fluorescence in situ hybridization were used to demonstrate that CPIO/pMIRNA-128 indeed expresses more miR-128 with the assisted magnetic field than without. In a biodistribution test, CPIO/Cy5-DNA showed higher accumulation at the tumor site where an external magnet is placed nearby.

Quantitative [Fe]MRI of PSMA-targeted SPIONs specifically discriminates among prostate tumor cell types based on their PSMA expression levels

“…The MRI data were taken at 1.0 T with recycle times ranging from 500 to 5,000 ms, and with echo times from 4 to 145 ms. A typical theoretical calculation of the T 1 w and T 2 w image contrast, and contrast difference, using the measured relaxivities of the µMACS SPIONs at 1.0 T and acquisition parameters within this range shows (Figure 2A) Figure 2B; [Fe] =0.0005051+0.03961 ∆C +0.009258 (∆C) 2 +0.008857 (∆C) 3 . While this inversion is straightforward to perform in Mathematica ® , it needs to be computed for each set of tissue, SPION, and acquisition parameters.…”

“…Such SPIONs loaded with therapeutic molecules, such as drugs, 2 microRNAs, 3 or shRNA, 4 are useful both as diagnostic and therapeutic agents, and an important, open question is how to accurately determine their concentrations in the target tissues in vivo, in a non-invasive manner. The direct methods that have been applied to SPION quantitation include both nonmagnetic schemes, such as positron emission tomography-computed tomography 5,6 and those utilizing the magnetic properties of the SPIONs, which include SQUID studies.…”

Manipulation of Schwann cell migration across the astrocyte boundary by polysialyltransferase-loaded superparamagnetic nanoparticles under magnetic field

“…38 SPIONs have been exploited for being amenable to manipulation by external magnetic forces for drug delivery, cell separation, and MRI. 39,40 The surface of SPIONs was further modified through the attachment of a cationic polymer, such as PEI, rendering it positively charged and thus apt for cellular internalization. [41][42][43] PEI-SPIONs could effectively absorb negatively charged PST plasmids via electrostatic attraction.…”

Trigger-Responsive Gene Transporters for Anticancer Therapy

“…Therefore, to release the nucleic acids, it is necessary to employ external triggers such as light, magnetic field, and US, along with a certain level of support from internal triggers such as protease and glutathione enzymes in the endosome/cytoplasm [48,49,50,51]. Table 1 elucidates the different triggers and its based gene transporters with their potential outcome in cancer gene therapy and also each of these triggers used for gene delivery are discussed in detail below:…”