pH-responsive sulfonamide/PEI system for tumor specific gene delivery: An in vitro study
pH-responsive sulfonamide/PEI system for tumor specific gene delivery: An in vitro study
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DOI：
10.1021/bm0503571
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发表时间：
2006-01-01
影响因子：
6.2
通讯作者：
Bae, YH
中科院分区：
文献类型：
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作者：
Sethuraman, VA;Na, K;Bae, YH
证明了有效靶向肿瘤酸性细胞外基质的 pH 敏感聚合物纳米颗粒的可行性。将质粒 DNA 与聚乙烯亚胺 (PEI) 复合，并进一步与 pH 敏感的二嵌段共聚物聚(甲基丙烯酰磺胺二甲氧嘧啶) (PSD)-block-PEG (PSD-b-PEG) 复合，以获得纳米颗粒。测试了纳米颗粒的屏蔽/去屏蔽以及生理和肿瘤 pH 下的细胞活力和转染效率。由DNA/PEI/PSD-b-PEG组成的纳米颗粒尺寸为300 nm，由于PSD-b-PEG对PEI的屏蔽，在pH 7.4下表现出低细胞毒性和转染性。 PSD-b-PEG与PEI/DNA复合物结合，减少了PEI正电荷与细胞的相互作用，使细胞毒性降低了60%。在 pH 6.6 时，纳米粒子表现出高细胞毒性和转染性，表明 PSD-b-PEG 从纳米粒子上脱离并允许 PEI 与细胞相互作用。 PSD-b-PEG能够识别正常组织和肿瘤组织之间pH值的微小差异，因此在靶向肿瘤区域的药物方面具有显着的潜力。
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.