Biotin-triggered release of poly(ethylene glycol)-avidin from biotinylated polyethylenimine enhances in vitro gene expression.
Covalently poly(ethylene glycol) (PEG)-ylated polyethylenimine (PEI)/pDNA complexes display prolonged blood circulation profiles compared with PEI/pDNA complexes, but such PEGylated particles may not be suitable for tumor targeting due to low interaction with cell membranes, low internalization, and low gene expression. Noncovalent PEGylation of cationic particles via PEG-avidin/biotin-PEI is an attempt to bridge the gap between the positive attributes of PEG (prolonged particle circulation) and the positive attributes of nontoxic cationic polymers (enhanced cell interactions) for greater gene expression. Our polymer, 2PEG-avidin/biotin-PEI8, forms salt-stable particles ( approximately 100 nm) under physiologic conditions with a minimum of two 2PEG-avidin molecules bound per polymer chain (biotin-PEI8, 8 biotins/PEI). Following 10 days of incubation with 3000-fold excess biotin, 2PEG-avidin completely dissociated from biotin-PEI8, and gene expression was increased 2.1-32-fold in various cell lines when the desirable transfection feature of the cationic polymer was retained. This new PEGylation approach has implications for generally improving the clinical aspect of gene delivery via a two-step therapeutic strategy: (1) intravenous injection of noncovalent PEG-avidin/biotin-polycation nanoparticles for prolonged circulation, followed by (2) temporal release of PEG-avidin from biotin-polycation through either endogenous biotin or intravenous injection of biotin.
Xiong
May P
MP
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, Wisconsin 53705-2222, USA.
Forrest
M Laird
ML
Karls
Angela L
AL
Kwon
Glen S
GS
D000818:Animals; D001360:Avidin / Q000737:chemistry / Q000378:metabolism*; D001710:Biotin / Q000737:chemistry; D019921:Biotinylation; D002478:Cells, Cultured; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry
D011073:Polyamines; C522257:di-(polyethylene glycol)-avidin-biotin-octa(ethyleneimine); D001360:Avidin; D011092:Polyethylene Glycols; D001710:Biotin; D011094:Polyethyleneimine