Intracellular Delivery of Poly(ethylene glycol) Conjugated Antisense Oligonucleotide Using Cationic Lipids by Formation of Self-Assembled Polyelectrolyte Complex Micelles

2006 ◽  
Vol 6 (9) ◽  
pp. 2790-2795 ◽  
Author(s):  
Ji Hoon Jeong ◽  
Sun Hwa Kim ◽  
Sung Wan Kim ◽  
Tae Gwan Park

A polyelectrolyte complex (PEC) micelle-based antisense oligodeoxynucleotide (ODN) delivery system was designed to overcome intrinsic limitations of cationic lipid-mediated gene transfer. Cationic lipid (Lipofectamine™, LF) and ODN conjugated poly(ethylene glycol) (PEG) were ionically complexed to form self-assembled spherical PEC micelles. They have a distinctive structural feature: a charge-neutralized core surrounded by highly flexible PEG corona. The PEC micelles could be visualized as a nano-sized sphere by atomic force microscopy (AFM). The DNA/LF PEC micelles exhibited far improved transfection efficiency compared to those of conventional lipoplex formulations (ODN/LF) in the presence of serum. They showed enhanced cellular uptake followed by rapid nuclear localization of ODN in human epithelial carcinoma (KB) cells. In addition, anti-proliferative activity of c-raf gene-directed antisense ODN was almost fully maintained in KB cells in the presence of serum.

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2553
Author(s):  
Jeffrey M. Ting ◽  
Alexander E. Marras ◽  
Joseph D. Mitchell ◽  
Trinity R. Campagna ◽  
Matthew V. Tirrell

A series of model polyelectrolyte complex micelles (PCMs) was prepared to investigate the consequences of neutral and zwitterionic chemistries and distinct charged cores on the size and stability of nanocarriers. Using aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization, we synthesized a well-defined diblock polyelectrolyte system, poly(2-methacryloyloxyethyl phosphorylcholine methacrylate)-block-poly((vinylbenzyl) trimethylammonium) (PMPC-PVBTMA), at various neutral and charged block lengths to compare directly against PCM structure–property relationships centered on poly(ethylene glycol)-block-poly((vinylbenzyl) trimethylammonium) (PEG-PVBTMA) and poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLK). After complexation with a common polyanion, poly(sodium acrylate), the resulting PCMs were characterized by dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). We observed uniform assemblies of spherical micelles with a diameter ~1.5–2× larger when PMPC-PVBTMA was used compared to PEG-PLK and PEG-PVBTMA via SAXS and DLS. In addition, PEG-PLK PCMs proved most resistant to dissolution by both monovalent and divalent salt, followed by PEG-PVBTMA then PMPC-PVBTMA. All micelle systems were serum stable in 100% fetal bovine serum over the course of 8 h by time-resolved DLS, demonstrating minimal interactions with serum proteins and potential as in vivo drug delivery vehicles. This thorough study of the synthesis, assembly, and characterization of zwitterionic polymers in PCMs advances the design space for charge-driven micelle assemblies.


Langmuir ◽  
2005 ◽  
Vol 21 (7) ◽  
pp. 2981-2987 ◽  
Author(s):  
Jonas Rundqvist ◽  
Jan H. Hoh ◽  
David B. Haviland

2007 ◽  
Vol 342-343 ◽  
pp. 425-428 ◽  
Author(s):  
Dhananjay Jere ◽  
Tae Hee Kim ◽  
Rohidas B. Arote ◽  
Hu Lin Jiang ◽  
Myung Haing Cho ◽  
...  

Vectors are vital aspect of gene delivery system which decides the success of gene therapy. Efficient transfection with minimum or no toxicity, are two principal aims of any gene delivery system. In this our study, we rationally developed biodegradable water soluble poly(ßamino ester) (PAE) based on spermine (SPR) and poly (ethylene glycol) (PEG), by Michael-type addition reaction and further studied for its potential as a gene carrier. Confirmation of synthesized PAE was done by proton NMR spectroscopy. In gel retardation assay, the PAEs have shown good DNA binding ability over wide range of polyplexes. The addition of PEG over SPR resulted in a novel PAE with higher degree of safety and transfection efficiency as compared with polyethylenimine 25K (PEI) when studied in 293T human kidney carcinoma cells.


Biomaterials ◽  
2013 ◽  
Vol 34 (15) ◽  
pp. 3795-3806 ◽  
Author(s):  
Keren Miller ◽  
Chiara Clementi ◽  
Dina Polyak ◽  
Anat Eldar-Boock ◽  
Liat Benayoun ◽  
...  

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