Targeting and Internalization of Liposomes by Bladder Tumor Cells Using a Fibronectin Attachment Protein-Derived Peptide-Lipopolymer Conjugate.
Targeting and Internalization of Liposomes by Bladder Tumor Cells Using a Fibronectin Attachment Protein-Derived Peptide-Lipopolymer Conjugate.
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使用纤连蛋白附着蛋白衍生的肽 - 脂聚合物结合物膀胱肿瘤细胞对脂质体的靶向和内在化。
DOI：
10.1021/acs.bioconjchem.7b00153
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发表时间：
2017-05-17
影响因子：
4.7
通讯作者：
Thompson DH
中科院分区：
文献类型：
--
作者：
Lee Y;Kischuk E;Crist S;Ratliff TL;Thompson DH
本文报道了一种合成的肽脂聚合物偶联物，它被掺入脂质体中以促进与膀胱肿瘤细胞周围的纤连蛋白（FBN）基质的特异性结合，并促进FBN-整联蛋白复合物的细胞内化。该肽以序列特异性和浓度依赖性方式促进与MB 49小鼠模型膀胱肿瘤细胞的结合，最大细胞结合发生在2 mol% RWFV-PEG 2000-DSPE。脂质体膜的双PEG化（即，4mol%mPEG1000-DSPE + 2 mol% RWFV-PEG 2000-DSPE）通过改善脂质体表面上的配体呈递而使结合增强> 1.6倍。肽-脂聚合物构建体的序列特异性通过比较含有RWFV-PEG 2000-DSPE的脂质体与乱序和非肽脂聚合物脂质体制剂来确认。携带MB 49肿瘤的小鼠在感兴趣的肿瘤相关区域中显示出FAP肽靶向脂质体比非靶向和乱序肽脂质体制剂更大的平均辐射值。这些发现表明，肽修饰的脂质体可能是一种有吸引力的载体，用于靶向递送到体内膀胱肿瘤。
A synthetic peptidolipopolymer conjugate, incorporated into liposomes to promote specific binding to the fibronectin (FBN) matrix surrounding bladder tumor cells and promote cellular internalization of FBN-integrin complexes, is reported. The peptide promotes association with MB49 mouse model bladder tumor cells in a sequence-specific and concentration-dependent manner, with the maximum cell association occurring at 2 mol% RWFV-PEG2000-DSPE. Double PEGylation of the liposome membrane (i.e., 4 mol% mPEG1000-DSPE + 2 mol% RWFV-PEG2000-DSPE) enhanced binding by > 1.6-fold, by improving ligand presentation on the liposome surface. The sequence specificity of the peptide-lipopolymer construct was confirmed by comparing liposomes containing RWFV-PEG2000-DSPE with scrambled and non-peptidic lipopolymer liposomal formulations. MB49 tumor-bearing mice showed greater mean radiance values for FAP peptide-targeted liposomes in tumor-associated regions of interest than for non-targeted and scrambled peptide liposome formulations. These findings suggest that peptide-modified liposomes may be an attractive vehicle for targeted delivery to bladder tumors in vivo.
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影响因子：
--
作者：
Perche F;Torchilin VP
通讯作者：
Torchilin VP
影响因子：
7.5
作者：
Brandau, Sven;Suttmann, Henrik
通讯作者：
Suttmann, Henrik
影响因子：
6.4
作者：
CLAVEL, J;CORDIER, S;HEMON, D
通讯作者：
HEMON, D
影响因子：
3.1
作者：
RATLIFF, TL;MCCARTHY, R;BROWN, EJ
通讯作者：
BROWN, EJ
影响因子：
254.7
作者：
Jemal, A;Tiwari, RC;Thun, MJ
通讯作者：
Thun, MJ