Cell-penetrating peptide CGKRK mediates efficient and widespread targeting of bladder mucosa following focal injury.
Cell-penetrating peptide CGKRK mediates efficient and widespread targeting of bladder mucosa following focal injury.
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DOI：
10.1016/j.nano.2017.04.004
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Simberg D
中科院分区：
文献类型：
--
作者：
Griffin JI;Cheng SKK;Hayashi T;Carson D;Saraswathy M;Nair DP;Simberg D
膀胱是局部给药的一个有吸引力的靶点。膀胱粘膜（尿道）的屏障功能对小分子和纳米颗粒的渗透提出了挑战。我们发现，局灶性机械损伤的尿路上皮大大提高了膀胱内给药的细胞穿透肽CGKRK（Cys-Gly-Lys-Arg-Lys）的结合和渗透。值得注意的是，CGKRK结合到整个尿路上皮，并且肽能够渗透到肌肉层中。这种现象不依赖于膀胱内出血，也不是由炎症反应引起的。CGKRK在用乙醇破坏粘膜后也有效地渗透尿路上皮，这表明屏障功能的丧失是广泛结合和渗透的先决条件。我们进一步证明了CGKRK有效结合和渗透膀胱的能力可以应用于CGKRK缀合的纳米凝胶的粘膜靶向，以使模型有效载荷（罗丹明）能够有效和广泛地递送至膀胱粘膜。细胞穿透肽在粘膜局灶性损伤后与膀胱有效结合
The bladder presents an attractive target for topical drug delivery. The barrier function of the bladder mucosa (urothelium) presents a penetration challenge for small molecules and nanoparticles. We found that focal mechanical injury of the urothelium greatly enhances the binding and penetration of intravesically-administered cell-penetrating peptide CGKRK (Cys-Gly-Lys-Arg-Lys). Notably, the CGKRK bound to the entire urothelium, and the peptide was able to penetrate into the muscular layer. This phenomenon was not dependent on intravesical bleeding and was not caused by an inflammatory response. CGKRK also efficiently penetrated the urothelium after disruption of the mucosa with ethanol, suggesting that loss of barrier function is a prerequisite for widespread binding and penetration. We further demonstrate that the ability of CGKRK to efficiently bind and penetrate the urothelium can be applied towards mucosal targeting of CGKRK-conjugated nanogels to enable efficient and widespread delivery of a model payload (rhodamine) to the bladder mucosa. Cell penetrating peptide shows efficient binding to the bladder after focal injury to mucosa
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影响因子：
16.1
作者：
Chacko RT;Ventura J;Zhuang J;Thayumanavan S
通讯作者：
Thayumanavan S
影响因子：
2.1
作者：
Engler, H;Anderson, SC;Maneval, DC
通讯作者：
Maneval, DC
DOI：
10.1152/ajprenal.00307.2001
发表时间：
2002-08-01
影响因子：
4.2
作者：
Lavelle, J;Meyers, S;Zeidel, ML
通讯作者：
Zeidel, ML
影响因子：
12.4
作者：
Agemy, Lilach;Kotamraju, Venkata R.;Ruoslahti, Erkki
通讯作者：
Ruoslahti, Erkki
影响因子：
6.6
作者：
Chen, Fanghong;Zhang, Guangjian;See, William A.
通讯作者：
See, William A.