The application of nanoparticles in gene therapy and magnetic resonance imaging

Abstract

The combination of nanoparticles, gene therapy, and medical imaging has given rise to a new field known as gene theranostics, in which a nanobioconjugate is used to diagnose and treat the disease. The process generally involves binding between a vector carrying the genetic information and a nanoparticle, which provides the signal for imaging. The synthesis of this probe generates a synergic effect, enhancing the efficiency of gene transduction and imaging contrast. We discuss the latest approaches in the synthesis of nanoparticles for magnetic resonance imaging, gene therapy strategies, and their conjugation and in vivo application.

Fig. 1

Example of a magnetization curve for superparamagnetic hydrophilic nanoparticles.

Fig. 2

Chemical modification of surfactant structure rendering hydrophilic nanoparticles.

Fig. 3

TEM images of SPIOs: (a) hydrophobic nanoparticle, scale bar is 50 nm; (b) and (c) hydrophilic nanoparticle via oxidation, scale bars are 50 and 20 nm, respectively.

Fig. 4

Transmission electron microscopy (TEM) images of gold/iron oxide (core/hollow-shell) nanoparticles synthesized with different amounts of oleic acid. Molar ratio of oleylamine/oleic acid: (a) 1:0, (b) 1:0.1, (c) 1:0.3, and (d) 1:1. (Reproduced with permission from Shevchenko et al., Adv Mater, 2008, 20, 4323-4329).

Fig. 5

Delivery vectors used in gene therapy strategies.

Fig. 6

Two different gene therapy strategies.

Fig. 7

Clinical trials assessing gene therapy worldwide. Data obtained from http://www.wiley.co.uk/genmed/clinical/.

Fig. 8

Presentation of biotinilated USPIO-conjugated avidindisplaying baculovirus (Baavi). The nanobioconjugate structure is shown in the figure (a). Nanoparticle attachment to viral particles was confirmed by AFM (b). In-plane scale bar is shown at the bottom; out-of-plane scale (height) is demonstrated by the sliding color scale. (Reproduced with permission from Räty et al., Gene Therapy, 2006, 1440-1446).

Fig. 9

MRI of intraventricular biotinilated USPIO1Baavi delivery. Representative sequential transverse T₂ images are (a) compared to sequential adiabatic T₂*-weighted gradient echo MRI-weighted spinecho images and (b) 2 h after biotinilated USPIO-coated Baavi injection. Bright areas represent high signal intensity (such as cerebrospinal fluid in ventricles) and dark areas represent low signal intensity owing to the presence of the contrast agent. A marked signal loss is detectable in T₂*-weighted MRI images (a), showing that gradient echo imaging provides improved sensitivity. However, sensitivity appears sufficient and anatomical features are better preserved and delineated in (b). A superimposed anatomical reference map, together with spin echo image (c) of rat brain after Baavi1biotinilated USPIO, is also shown from one animal. In this composite, the ventricles are of high signal intensity (white) and brain regions are delineated by gray lines. (Reproduced with permission from Räty et al., Gene Therapy, 2006, 1440-1446).

Fig. 10

Adenovirus-MnMEIO nanobioconjugates for targeted MRI and gene delivery: (a) TEM image of the nanobioconjugate; (b) Targeting and gene delivery processes; (c) Such events are imaged only in the CAR-positive cells by a dark contrast in MRI and the GFP expression; (d) TEM image of the nanoprobe-treated U251N cells. Solid circles indicate nanoprobes either under endocytosis or trapped inside endosomes. Dashed circles indicate some nanoprobes found near the nuclear membrane. (Reproduced with permission from Huh et al., Adv Mater, 2007, 19, 3109-3112).