Tissue-specific gene delivery via nanoparticle coating

Abstract

The use of biomaterials for gene delivery can potentially avoid many of the safety concerns with viral gene delivery. However, the efficacy of polymeric gene delivery methods is low, particularly in vivo. One significant concern is that the interior and exterior composition of polymeric gene delivery nanoparticles are often coupled, with a single polymer backbone governing all functions from biophysical properties of the polymer/DNA particle to DNA condensation and release. In this work we develop electrostatically adsorbed poly(glutamic acid)-based peptide coatings to alter the exterior composition of a core gene delivery particle and thereby affect tissue-specificity of gene delivery function in vivo. We find that with all coating formulations tested, the coatings reduce potential toxicity associated with uncoated cationic gene delivery nanoparticles following systemic injection. Particles coated with a low 2.5:1 peptide:DNA weight ratio (w/w) form large 2 micron sized particles in the presence of serum that can facilitate specific gene delivery to the liver. The same particles coated at a higher 20:1 w/w form small 200 nm particles in the presence of serum that can facilitate specific gene delivery to the spleen and bone marrow. Thus, variations in nanoparticle peptide coating density can alter the tissue-specificity of gene delivery in vivo.

Nanodentistry: Combining Nanostructured Materials and Stem Cells for Dental Tissue Regeneration

“…n Targeting therapy: gene, protein & drug intracellular delivery One of the most attractive concepts in manipulating the fate of stem cells and directing their differentiation into specific cell populations is the use of nanomaterials for intracellular gene delivery (e.g., RNAi and DNA) [91,92]. Generally, viral (e.g., adenoviruses, lentiviruses and retroviruses) and nonviral vectors (e.g., lipids and polymers) can be used for cellular transfection and/or nucleofection, thus offering durable gene expression within stem cells [93][94][95][96].…”

Advanced Drug Carriers Targeting Bone Marrow

“…Harris and co-workers studied tissue-specific gene delivery via nanoparticle coating (Harris et al, 2010). They prepared cationic nanoparticles with plasmid DNA and then coated their cationic surface with poly anionic poly(glutamic acid)-based peptides with and without cationic insert.…”

“…This importance suggests that the phagocytic activity of bone marrow is a potent target of nanoparticle-based drug delivery. In fact, it has been demonstrated that nanoparticles modified with a specific molecule on their surface are distributed selectively into bone marrow tissues (Harris et al 2010;Mann et al, 2011;Moghimi, 1995;Porter et al, 1992;Schettini et al, 2006;Sou et al 2007Sou et al , 2010Sou et al , 2011a. These bone marrow-specific drug carrier systems are expected to improve diagnostic and therapeutic systems to treat hematopoietic disorders.…”

“…Also flow cytometry analysis is a useful method to determine the targeted cell population quantitatively (Harris et al, 2010). In this method, bone marrow cells will be labeled with markers to identify specific cell subtypes.…”

Fluorescent Labeling of Plasmid DNA and mRNA: Gains and Losses of Current Labeling Strategies

“…AlexaFluor 680 -pDNA 44 . This versatility was also employed to make biotinylated plasmids 43 for in vivo transfection with Lac-PEI.…”