pH-Responsive Sulfonamide/PEI System for Tumor Specific Gene Delivery:  An in Vitro Study

• Published in: Biomacromolecules Vol. 7; no. 1; pp. 64 - 70
• Main Authors: Sethuraman, Vijay A, Na, Kun, Bae, You Han
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-01-2006
• Subjects: Applied sciences; Biological and medical sciences; Cations - chemistry; Cell Line, Tumor; Cell Survival - drug effects; DNA - chemistry; Drug Delivery Systems; Exact sciences and technology; Forms of application and semi-finished materials; General pharmacology; Genes, Reporter - genetics; Humans; Hydrogen-Ion Concentration; Medical sciences; Microscopy, Atomic Force; Miscellaneous; Molecular Structure; Nanostructures - chemistry; Neoplasms - genetics; Neoplasms - pathology; Organ Specificity; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasmids - genetics; Plasmids - ultrastructure; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacology; Polyethyleneimine - chemistry; Polyethyleneimine - pharmacology; Polymer industry, paints, wood; Sulfonamides - chemistry; Sulfonamides - pharmacology; Technology of polymers; Transfection - instrumentation; Transfection - methods; Particle size; Targeting; Nanoparticle; Cytotoxicity; Drug carrier; Lateral group; Sulfadimethoxine; pH; Extracellular matrix; Electrokinetic potential; Interpolymer; Tumor cell; Ternary complex; Control release polymer; Particle suspension; Ethylene oxide copolymer; Experimental study; In vitro; Genetic transfer; Plasmid; Polyelectrolyte; Methacrylamide derivative copolymer; Cell line; Ionic strength; DNA; Diblock copolymer; Gene therapy; Polyethylene imine
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm0503571

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.