title: pH-responsive sulfonamide/PEI system for tumor specific gene delivery: an in vitro study.
abstract: The feasibility of pH-sensitive polymeric nanoparticles that effectively target the acidic extracellular matrix of tumors is demonstrated. Plasmid DNA was complexed with polyethyleneimine (PEI) and further with a pH-sensitive diblock copolymer, poly(methacryloyl sulfadimethoxine) (PSD)-block-PEG (PSD-b-PEG), to obtain naonparticles. The shielding/deshielding of nanoparticles was tested along with cell viability and transfection efficiency at physiological and tumor pH. The nanoparticles composed of DNA/PEI/PSD-b-PEG were 300 nm in size and showed low cytotoxicity and transfection at pH 7.4 due to shielding of PEI by PSD-b-PEG. The PSD-b-PEG bound to PEI/DNA complex decreased the interaction of PEI positive charges with cells and reduced the cytotoxicity by 60%. At pH 6.6, the nanoparticles demonstrated high cytotoxicity and transfection, indicating PSD-b-PEG detachment from the nanoparticles and permit PEI to interact with cells. PSD-b-PEG is able to discern the small difference in pH between normal and tumor tissues and hence has remarkable potential in drug targeting to tumor areas.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, UT 84108, USA.
authors.forename: Vijay A
authors.initials: VA
authors.lastname: Sethuraman
authors.forename: Kun
authors.initials: K
authors.lastname: Na
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
mesh_terms: D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D016503:Drug Delivery Systems; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009928:Organ Specificity; D010316:Particle Size; D010957:Plasmids / Q000235:genetics / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry* / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology; D014162:Transfection / Q000295:instrumentation* / Q000379:methods*
chemical_list: D002412:Cations; D013449:Sulfonamides; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA