Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Jialiang Xia
  • Huayu Tian
  • Xuesi Chen

Detail(s)

Original languageEnglish
Pages (from-to)45-53
Journal / PublicationActa Biomaterialia
Volume26
Online published17 Aug 2015
Publication statusPublished - 15 Oct 2015

Abstract

A novel pH-responsive gene delivery system for tumor acidity-targeted pDNA delivery is prepared by introducing a rapid charge-conversional zwitterionic copolymer to the positive surface of PEI/pDNA complexes through electrostatic interaction. The shielding system (OEAL) consists of oligoethylenimine (OEI), poly(L-aspartate) (PBLA), and poly(L-lysine) (PLL). The charge-conversional behavior of the OEAL/PEI/DNA ternary complex is evaluated by zeta potential assay. The surface charges of the complexes can change from negative to positive in the pH range of 7.4-6.8. Under a simulative in vivo environment, OEAL/PEI/DNA exhibits promotion of cellular uptake by tumor cells and enhanced gene transfection efficiency because of its good charge-conversional properties. Antitumor experiments further show that the pH-responsive charge-conversional system can mediate a therapeutic gene that can induce tumor apoptosis (pKH3-rev-casp-3) to achieve effective tumor inhibition. Accordingly, OEAL can be regarded as a promising tumor microenvironment-sensitive gene delivery shielding system for antitumor therapy.

Statement of Significance

This manuscript focused on the novel pH-responsive gene delivery system for tumor acidity-targeted pDNA delivery. The novel system is prepared by introducing a rapid charge-conversional zwitterionic copolymer, consisting of oligoethylenimine, poly(L-aspartate) and poly(L-lysine), to the positive surface of PEI/pDNA complexes. The surface charges of the complexes can change from negative to positive from pH 7.4 to 6.8. OEAL/PEI/DNA shows promoting cellular uptake by tumor cells and enhanced gene transfection efficiency. The antitumor experiments further show that the pH responsive charge conversional system can mediate pKH3-rev-casp-3 to achieve effective tumor inhibition. Accordingly, OEAL can be regarded as a promising tumor microenvironment sensitive gene delivery shielding system for antitumor therapy.

Research Area(s)

  • Cell apoptosis, Charge conversion, pH-responsive, Rev-caspase-3, Tumor therapy, GENE TRANSFECTION, SIRNA DELIVERY, IN-VIVO, CARRIERS, THERAPY, EFFICIENT, NANOPARTICLES, CELLS, POLYETHYLENIMINE, METASTASIS

Citation Format(s)

Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment. / Chen, Jie; Dong, Xuan; Feng, Tianshi; Lin, Lin; Guo, Zhaopei; Xia, Jialiang; Tian, Huayu; Chen, Xuesi.

In: Acta Biomaterialia, Vol. 26, 15.10.2015, p. 45-53.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review