期刊
EXPERT OPINION ON DRUG DELIVERY
卷 17, 期 3, 页码 395-405出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425247.2020.1723544
关键词
Targeted liposomes; ATB0; S; cellular uptake; drug delivery; pancreatic cancer
资金
- National Natural Science Foundation of China [81803443, 81903551]
- Natural Science Foundation of Zhejiang Province [LQ19H300001]
- Wenzhou Science and Technology Bureau [ZY2019007, Y20180180, Y20180208, Y20190177]
- Second Affiliated Hospital of Wenzhou Medical University
- Yuying Children's Hospital of Wenzhou Medical University
Background: SLC6A14 (ATB(0,+)), a Na+/Cl(-)coupled transporter for neutral/cationic amino acids, is overexpressed in many cancers; It has been investigated as a target for improved liposomal drug delivery to treat liver cancer. Research design and methods: Here we explored the mechanism of ATB(0,+)-mediated entry of such liposomes. As ATB(0,+) is highly expressed in pancreatic cancer, we also examined the therapeutic utility of ATB(0,+)-targeted liposomal drug delivery to treat this cancer. Results: The uptake of lysine-conjugated liposomes (LYS-LPs) was greater in ATB(0,+)-positive MCF7 cells. The uptake process consisted of two steps: binding and internalization. The binding of LYS-LPs to MCF7 cells was higher than that of bare liposomes, and the process was dependent on Na+ and Cl-, and inhibitable by ATB(0,+) substrates or blocker. In contrast, the internalization step was independent of lysine. The cellular entry of LYS-LPs facilitated by ATB(0,+) occurred via endocytosis with transient endosomal degradation of ATB(0,+) protein with subsequent recovery. Moreover, LYS-LPs also enhanced the uptake and cytotoxicity of gemcitabine in these cells in an ATB(0,+)-dependent manner. Conclusions: We conclude that ATB(0,+) could be exploited for targeted drug delivery in the form of lysine-conjugated liposomes and that the approach represents a novel strategy for enhanced pancreatic cancer therapy.
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