Structure Reconstruction of LyP-1: (L)c(LyP-1) Coupling by Amide Bond Inspires the Brain Metastatic Tumor Targeted Drug Delivery
Structure Reconstruction of LyP-1: (L)c(LyP-1) Coupling by Amide Bond Inspires the Brain Metastatic Tumor Targeted Drug Delivery
复制标题
LyP-1 的结构重建：(L)c(LyP-1) 酰胺键偶联激发脑转移瘤靶向药物递送
DOI：
10.1021/acs.molpharmaceut.7b00801
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发表时间：
2018
影响因子：
4.9
通讯作者：
Lu Weiyue
中科院分区：
文献类型：
--
作者：
Zhang Xiaoyu;Wang Fei;Shen Qing;Xie Cao;Liu Yu;Pan Jun;Lu Weiyue
The stability and binding affinity of targeting ligands are very important in active targeting drug delivery. Herein we used LyP-1 peptide as a model peptide to investigate chemical–biology-based strategies in the design of peptide ligands for active targeting. LyP-1 is a short peptide cyclized with a disulfide bond. It can specifically bind to tumor cells and tumor lymphatics through the interaction with cell-surface protein p32/gC1qR.Lc(LyP-1), with a same sequence of LyP-1, is coupled by amide bond. It showed better cellular uptake and stability in blood in our previous research. Further, usuallyd-peptide demonstrates higher stability thanl-peptide, and it may contribute to better active targeting abilityin vivo. Herein, we designed a retro-inverso isomer ofLc(LyP-1), termedDc(LyP-1), expecting to inspire brain metastatic tumor targeted drug delivery. However, althoughLc(LyP-1) showed lower stability thanDc(LyP-1) in fresh rat bold serum, both the 4T1 cellular uptake capacity (89.20%) and p32 protein binding affinity (7.39 × 10–6) were significantly higher than those (33.41%, 1.37 × 10–5) ofDc(LyP-1). Further,Lc(LyP-1) modified PEG–PLA micelles displayed much higherin vivodistribution in brain metastatic tumor thanDc(LyP-1). All results suggested thatLc(LyP-1) had a better performance thanDc(LyP-1) in brain metastatic tumor-targeted drug delivery.
