Imidazolyl-PEI modified nanoparticles for enhanced gene delivery.
The derivatives of polyethylenimine (PEI 25 and 750kDa) were synthesized by partially substituting their amino groups with imidazolyl moieties. The series of imidazolyl-PEIs thus obtained were cross-linked with polyethylene glycol (PEG) to get imidazolyl-PEI-PEG nanoparticles (IPP). The component of hydrophobicity was introduced by grafting the lauryl groups in the maximal substituted IPP nanoparticles (IPPL). The nanoparticles were characterized with respect to DNA interaction, hydrodynamic diameter, zeta potential, in vitro cytotoxicity and transfection efficiency on model cell lines. The IPP and IPPL nanoparticles formed a loose complex with DNA compared to the corresponding native PEI, leading to more efficient unpackaging of DNA. The DNA loading capacity of IPP and IPPL nanoparticles was also lower compared to PEI. The imidazolyl substitution improved the gene delivery efficiency of PEI (750kDa) by nine- to ten-fold and PEI (25kDa) by three- to four-fold. At maximum transfection efficiency, the zeta potential of nanoparticles was positive after forming a complex with DNA. The maximum level of reporter gene expression was mediated by IPPL nanoparticles in both the series. The cytotoxicity, another pertinent problem with cationic polymers, was also negligible in case of IPP and IPPL nanoparticles.
Swami
Archana
A
Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, Delhi 110007, India.
Aggarwal
Anita
A
Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, Delhi 110007, India.
Pathak
Atul
A
Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, Delhi 110007, India.
Patnaik
Soma
S
Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, Delhi 110007, India.
Kumar
P
P
Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, Delhi 110007, India.
Singh
Y
Y
Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, Delhi 110007, India.
Gupta
K C
KC
Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, Delhi 110007, India. Electronic address: kcgupta@igib.res.in.
D021581:Active Transport, Cell Nucleus; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002522:Chlorocebus aethiops; D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D007097:Imines / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D007850:Lauric Acids / Q000737:chemistry; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011095:Polyethylenes / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D014162:Transfection / Q000379:methods*
D003432:Cross-Linking Reagents; D007093:Imidazoles; D007097:Imines; D007850:Lauric Acids; D011095:Polyethylenes; C505405:poly(ethylene imine); C030358:lauric acid; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D004247:DNA