Multifunctional Envelope-Type Nano Device: Evolution from Nonselective to Active Targeting System

Abstract

A paradigm shift has occurred in the field of drug delivery systems (DDS), one being intracellular targeting, and the other, active targeting. An important aspect of intracellular targeting involves delivering nucleic acids such as siRNA/pDNA rather than small molecular compounds, since the mechanism responsible for their entering a target cell is usually via endocytosis, and the efficiency of endosomal escape is a critical factor in determining the functional activities of siRNA/pDNA. A multifunctional envelope-type nano device (MEND) was developed to control the intracellular trafficking of nano carriers containing siRNA/pDNA. An octaarginine (R8) modified MEND was developed to achieve this. Considerable progress has been made in active targeting to selective tissue vasculature such as tumor, adipose tissue, and the lung where endothelial barrier is tight against nanoparticles with diameters larger than 50 nm. A dual-ligand system is proposed to enhance active targeting ability by virtue of a synergistic interaction between a selective ligand and a cell penetrating ligand. Prohibitin targeted nanoparticles (PTNP) were developed to target endothelial cells in adipose tissue, which deliver apoptotic peptides/proteins to the adipose vasculature. Lung endothelial cells can be targeted by means of the GALA peptide, which is usually used to enhance endosomal escape. These active targeting systems can induce pharmacological effects in in vivo conditions. Finally, a novel strategy for producing an original ligand has been developed, especially for the tumor vasculature. This progress in DDS promises to extend the area of nanomedicine as a breakthrough technology.

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination

“…DOTAP/Chol/DSPE-PEG-2000 forms a cationic lipid shell, and CHEMS/DOPE/R8 is a lipid shell with an active targeting moiety; both have previously been applied for RNA delivery (26, 27). DC2.4 served as the antigen presenting cells and mRNA molecules encoding the eGFP protein was applied to prepare the polyplex core.…”

The delivery of therapeutic oligonucleotides

“…Another promising study used a cationic peptide derived from bee melittin to form nanocomplexes with siRNA directed against NF-kB; these were used to treat a mouse model of rheumatoid arthritis (210). In addition to their direct use as polyplexes, CPPs have been used to augment the properties of other delivery systems such as LNPs (211). An interesting variant of the CPP approach entailed making a chimera of an RNA binding protein and a CPP.…”

Dual‐peptide functionalized nanoparticles for therapeutic use

“…[78] Interestingly, the lysine residues of the cell penetrating peptide were Hayashi et al synthesized two distinct liposomes both containing a polyarginine peptide for cell penetration, one targeting liver disease through the GALA peptide and the other targeting cancer through the RGD peptide. [58] They found that by adding the R8 peptide onto the GALA bearing liposomes there was a 100-fold increase in pDNA delivery to the liver compared to the control. Further, when R8 was added to the RGD bearing liposome the dual peptide liposome had twice as much cell uptake compared to either single peptide liposome controls.…”