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The development of techniques to efficiently deliver genes using nonviral approaches can broaden the application of gene delivery in medical applications without the safety concerns associated with viral vectors. Here, we designed a clustered integrin-binding platform to enhance the efficiency and targetability of nonviral gene transfer to HeLa cells with low and high densities of αvβ3 integrin receptors. Arg-Gly-Asp (RGD) nanoclusters were formed using gold nanoparticles functionalized with RGD peptides and used to modify the surface of DNA/poly(ethylene imine) (PEI) polyplexes. DNA/PEI polyplexes with attached RGD nanoclusters resulted in either 5.4- or 35-fold increase in gene transfer efficiency over unmodified polyplexes for HeLa cells with low- or high-integrin surface density, respectively. The transfection efficiency obtained with the commercially available vector jetPEI-RGD was used for comparison as a vector without clustered binding. JetPEI-RGD exhibited a 1.2-fold enhancement compared to unmodified jetPEI in cells with high densities of αvβ3 integrin receptors. The data presented here emphasize the importance of the RGD conformational arrangement on the surface of the polyplex to achieve efficient targeting and gene transfer, and provide an approach to introduce clustering to a wide variety of nanoparticles for gene delivery.Molecular Therapy (2009) 17 5, 828–836 doi:10.1038/mt.2009.11 [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis is an important cause of restrictive cardiomyopathy and congestive heart failure. Bone scintigraphy with [Tc]hydroxymethylene diphosphonate (Tc-HDP) and [F]sodium fluoride (F-NaF) have been investigated in the noninvasive diagnosis of transthyretin (ATTR)-related cardiac amyloidosis. We present a case of a 76-year-old man with metastatic prostate cancer who underwent Tc-HDP bone scintigraphy with an incidental finding of diffuse left ventricular abnormal uptake suggesting ATTR cardiac amyloidosis. Review of previous imaging showed a negative F-NaF PET/CT study. This example suggests that the mechanism of uptake of Tc-HDP and F-NaF may differ in patients with ATTR cardiac amyloidosis.

The present report describes the synthesis and biological evaluation of a molecular imaging platform based on gold nanoparticles directly labeled with indium-111. The direct labeling approach facilitated radiolabeling with high activities while maintaining excellent stability within the biological environment. The resulting imaging platform exhibited low interference of the radiolabel with targeting molecules, which is highly desirable for in-vivo probe tracking and molecular targeted tumor imaging. The indium-111 labeled gold nanoparticles were synthesized using a simple procedure that allowed stable labeling of the nanoparticle core with various indium-111 activities. Subsequent surface modification of the particle cores with RGD-based ligands at various densities allowed for molecular targeting of the αvß3 integrin in-vitro and for molecular targeted imaging in human melanoma and glioblastoma models in-vivo. The results demonstrate the vast potential of direct labeling with radioisotopes for tracking gold nanoparticles within biological systems., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The ability to genetically modify mesenchymal stem cells (MSCs) seeded inside synthetic hydrogel scaffolds would offer an alternative approach to guide MSC differentiation. In this report, we explored gene transfer to MSCs seeded on top or inside matrix metalloproteinase (MMP) degradable hydrogels that were loaded with DNA/poly(ethylene imine) (PEI) polyplexes. DNA/PEI polyplexes were encapsulated inside poly(ethylene glycol) (PEG) hydrogels crosslinked with MMP degradable peptides via Michael Addition chemistry. Gene transfer was visualized and quantified through using a vector encoding for green fluorescent protein and luciferase. We found that gene transfer to MSCs was possible for cells seeded both in two and three dimensions. The amount of luciferase expression was similar for cells seeded in two and three dimensions even though the number of cells in three dimensions is significantly higher, indicating that gene transfer to cells seeded in two dimensions is more efficient than for cells seeded in three dimensions. The use of hydrogel scaffolds that allow cellular infiltration to deliver DNA may result in long-lasting signals in vivo, which are essential for the regeneration of functional tissues.