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

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• 作者：Vijay A. Sethuraman ; Kun Na ; and You Han Bae
• 刊名：Biomacromolecules
• 出版年：2006
• 出版时间：January 2006
• 年：2006
• 卷：7
• 期：1
• 页码：64 - 70
• 全文大小：512K
• 年卷期：v.7,no.1(January 2006)
• ISSN：1526-4602

文摘

The feasibility of pH-sensitive polymeric nanoparticles that effectively target the acidic extracellular matrix oftumors 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 obtainnaonparticles. The shielding/deshielding of nanoparticles was tested along with cell viability and transfectionefficiency at physiological and tumor pH. The nanoparticles composed of DNA/PEI/PSD-b-PEG were 300 nm insize 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 thecytotoxicity by 60%. At pH 6.6, the nanoparticles demonstrated high cytotoxicity and transfection, indicatingPSD-b-PEG detachment from the nanoparticles and permit PEI to interact with cells. PSD-b-PEG is able to discernthe small difference in pH between normal and tumor tissues and hence has remarkable potential in drug targetingto tumor areas.