文献类型：期刊文献

英文题名：pH-Triggered copolymer micelles as drug nanocarriers for intracellular delivery

作者：Hao, Weiju[1,2];Liu, Danyang[1,2];Shang, Yazhuo[1,2];Zhang, Junqi[3,4];Xu, Shouhong[1,2];Liu, Honglai[1,2]

机构：[1]E China Univ Sci & Technol, Key Lab Adv Mat, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Dept Chem, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Fudan Univ, Minist Hlth, Key Lab Med Mol Virol, 138 Yixueyuan Rd, Shanghai 200032, Peoples R China;[4]Fudan Univ, Minist Educ, Dept Med Microbiol & Parasitol, Sch Basic Med Sci, 138 Yixueyuan Rd, Shanghai 200032, Peoples R China

年份：2016

卷号：6

期号：35

起止页码：29149

外文期刊名：RSC ADVANCES

收录：;EI(收录号：20182305270326);WOS:【SCI-EXPANDED(收录号:WOS:000373029500015)】；

基金：Financial support for this work was provided by the National Natural Science Foundation of China (No. 21276074), the 111 Project (No. B08021) of China and the Fundamental Research Funds for the Centre Universities of China.

语种：英文

外文关键词：Cells - Targeted drug delivery - pH sensors - Controlled drug delivery - Cell culture

摘要：One growing issue is how to use the weakly acidic conditions in endosomes/lysosomes for designing highly pH-sensitive drug carriers to deliver chemotherapeutic drugs accurately. In this paper, pH-sensitive amphiphilic triblock copolymers PEG(8)-PDPA(n)-PEG(8) (n = 30, 50 and 100) were synthesized. Micelles composed of the copolymers were found to enter into lysosomes using a lysosome tracker method. The pH-sensitivity makes the micelles stable at pH 7.4 but swell and become looser at pH 6.0 due to protonation. Then, doxorubicin (DOX) was efficiently encapsulated in the hydrophobic cores of the micelles and released continuously in a weakly acidic environment. Cell toxicity assays were carried out using 2 human cell lines (HEK293 and Huh7) and showed good cyto-compatibility. In vitro cell viability tests proved that the DOX-loaded micelles could be more efficiently taken up by Huh7 tumor cells than free DOX, as well as actively trigger intracellular DOX release. Furthermore, in addition to small molecules (DOX), the copolymer micelles could also deliver macromolecules (such as transferrin, which could not enter into cells by itself) into lysosomes/endosomes. These nontoxic and multifunctional micelles can serve as a promising treatment candidate for efficient intracellular drug delivery and realtime monitoring.