Heat-shrinking DNA nanoparticles for in vivo gene delivery

The reduced‐charge melittin analogue MelP5 improves the transfection of non‐viral DNA nanoparticles

“…The present study advances our previous work on polyacridine (PAcr)-melittin conjugate in vitro gene delivery 11 , using a previously optimized polyacridine peptide (PAcr) for in vivo gene delivery [17][18][19] (Figure 1A). MelP5, Mac70, and melittin PAcr conjugates (Figure 1B) gWiz-Luc, a 6,732-bp luciferase-expressing plasmid under the control of a cytomegalovirus (CMV) promoter was obtained from Aldevron (Fargo, ND) and pGL3 control vector, a 5,256-bp luciferase-expressing plasmid under the control of the SV40 promoter and enhancer, as well as the ONE-Glo luciferase assay, were from Promega (Madison, WI).…”

“…Second, the lower cationic charge of MelP5 may be more beneficial for in vivo biodistribution and activity, since these gene delivery systems rely on the careful control of nanoparticle surface groups and charge or zeta potential. 18,20,33 Addition of melittin to a gene delivery system may compromise a nanoparticle's biophysical properties and result in aberrant biodistribution. Finally, this study identifies reducible PEGylation as a key parameter for effective gene delivery with polyacridine peptides.…”

“…where "Acr" refers to Nε-(9-acridinyl)lysine, was synthesized as described previously. 11,17,18 Peptides were cleaved from the resins and sidechains deprotected with TFA/EDT/water (95:2.5:2.5, v/v/v) for 2-3 h at room temperature (RT), followed by filtration and precipitation in ice-cold diethyl ether. Crude peptides were pelleted by centrifugation, lyophilized, and stored frozen in 0.1% (v/v) TFA in water.…”

“…22 All three analogues were conjugated to a polyacridine peptide (PAcr) previously optimized for DNA binding, compaction, and stability through in vivo structure-activity analysis. [17][18][19] A key design feature was the linkage of PAcr and melittin analogue through a disulfide bond to allow for reductive release and activation of pore forming activity (Figure 1A). 11 This was accomplished by synthesizing the melittin analogues with an ortho-pyridyl disulfide (OPSS)activated Cys residue for directed disulfide exchange with PAcr (Table 1).…”

Macrophage membrane coated nanoparticles: a biomimetic approach for enhanced and targeted delivery

“…Nanotherapeutics have provided a solution for various inevitable problems in the biomedical arena due to their unique properties of efficient drug loading and subsequent release, delivery of hydrophobic drugs and multiple endocytic routes. [1][2][3] These unique characteristics of nanomaterials integrate them in drug delivery, 4,5 gene delivery, 6,7 vaccination 8,9 and antimicrobial properties. 10,11 In the last three decades, almost 40 nanomaterial based medicines have entered into clinical trials and most of them are used in cancer imaging which provides rapid, longitudinal and non-invasive visualization.…”