Self-assembling micelle-like nanoparticles based on phospholipid–polyethyleneimine conjugates for systemic gene delivery

Abstract

With few exceptions, where local administration is feasible, progress towards broad clinical application of gene therapies requires the development of effective delivery systems. Here we report a novel non-viral gene delivery vector, ‘micelle-like nanoparticle’ (MNP) suitable for systemic application. MNP were engineered by condensing plasmid DNA with a chemical conjugate of phospholipid with polyethylenimine (PLPEI) and then coating the complexes with an envelope of lipid monolayer additionally containing polyethylene glycol-phosphatidyl ethanolamine (PEG-PE), resulting in spherical ‘hard-core’ nanoparticles loaded with DNA. MNP allowed for complete protection of the loaded DNA from enzymatic degradation, resistance to salt-induced aggregation, and reduced cytotoxicity. MNP also demonstrated prolonged blood circulation and low RES accumulation. Intravenous injection of MNP loaded with plasmid DNA encoding for the Green Fluorescence Protein (GFP) resulted in an effective transfection of a distal tumor. Thus, MNP provide a promising tool for systemic gene therapy.

Nanomedicine in pulmonary delivery

“…100 To solve these problems, various modifications of PEI with liposomes/PEGs or conjugations of PEI with ligands such as transferrin have been investigated extensively. [101][102][103][104][105][106][107] Noninvasive pulmonary gene delivery using cationic polymers has been reviewed in detail elsewhere. 95 …”

Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

“…4,6 The number of hydrophilic EO (x) and hydrophobic PO (y) units can be altered, and the retention of the block copolymer in the organs increases as the length of the hydrophobic PO block increases, or as the hydrophiliclipophilic balance (HLB) value decreases. Kabanov and other researchers [12][13][14] reported that Pluronic could enhance cell interactions, DNA transport, and transgene expression, and that Pluronics possess the unique ability to incorporate themselves into cell membranes in the presence of the hydrophobic poly(propylene oxide) chain. In contrast, the hydrophilic EO chain does not interact with lipid membranes but it could be used to prevent the binding of other polymers with the membranes.…”

Novel dipeptide nanoparticles for effective curcumin delivery

“…[22][23][24][25][26][27] Several reports, including our own studies, have shown that dipeptides, either free or with N-or C-terminal modifications, can self-assemble into well-defined NPs. 18,19,[28][29][30] However, most of these studies have shown assembly in an aqueous environment and may not be suitable for delivering hydrophobic bioactive molecules.…”

“…In DLS studies, (Cm)NPs exhibited an Rh of approximately 160 nm and PDI of 0.1 ( Figure 5A), which is comparable to other reported nanoformulations of curcumin used for delivery purposes. [39][40][41][42] Since tumors, due to their leaky vasculature and poor lymphatic drainage, usually take up 10-500-nm particles, 26,54 the given size of (Cm) NPs is advantageous for their passive targeting to tumor tissues. TEM analysis further revealed that (Cm)NPs were much more regular and stable compared to those without the drug (Figures 5B vs 3B).…”