Arginine conjugation affects the endocytic pathways of chitosan/DNA nanoparticles

作者：Zhang, Hailing; Zhu, Dunwan; Song, Liping; Liu, Lanxia; Dong, Xia; Liu, Zhenbao; Leng, Xigang^*

来源：Journal of Biomedical Materials Research Part A, 2011, 98A(2): 296-302.

DOI：10.1002/jbm.a.33115

• chitosan
• nanoparticle
• endocytic pathway
• arginine
• gene delivery

Previous reports showed that arginine-rich peptides and oligoarginines facilitated the cellular internalization of DNA and proteins. A number of studies demonstrated that arginine-conjugated chitosan (CS)/DNA nanoparticles (ACGN) mediated significantly higher expression of the transgenes when compared with CS/DNA nanoparticles (CGN). However, the underlying mechanisms remain poorly understood. In the current study, the endocytic pathways through which cells internalize ACGN and CGN were explored by incubating the fluorescent CGN or ACGN with A10 cells in the presence of a variety of inhibitors of different endocytic pathways. The data accumulated in the current study revealed that conjugation of arginine moieties onto CS molecules enhanced the cellular uptake of the polymer/DNA nanoparticles and their transgenic efficacy, probably due to changes in the endocytic pathways, which led to the preference of internalization of ACGN by the caveolin-mediated endocytosis in comparison with that of CGN. These findings provide further support to the previous observations that ACGN mediated much higher expression of the transgenes when compared with CGN.

• 出版日期2011-8
• 单位中国医学科学院北京协和医院; 北京协和医学院