کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
877367 | 911018 | 2016 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles](/preview/png/877367.png)
A single chain polypeptide containing the low density lipoprotein receptor (LDLR) ligand Seq-1 with blood–brain barrier (BBB) crossing activity has been successfully modified by conventional genetic engineering to self-assemble into stable protein-only nanoparticles of 30 nm. The nanoparticulate presentation dramatically enhances in vitro, LDLR-dependent cell penetrability compared to the parental monomeric version, but the assembled protein does not show any enhanced brain targeting upon systemic administration. While the presentation of protein drugs in form of nanoparticles is in general advantageous regarding correct biodistribution, this principle might not apply to brain targeting that is hampered by particular bio-physical barriers. Irrespective of this fact, which is highly relevant to the nanomedicine of central nervous system, engineering the cationic character of defined protein stretches is revealed here as a promising and generic approach to promote the controlled oligomerization of biologically active protein species as still functional, regular nanoparticles.
Protein engineering at predefined amino acid positions has been proved useful to convert, a LDLR-targeted single chain polypeptide, into self-assembling building blocks of protein-only nanoparticles. These entities self-assemble spontaneously, show improved cell penetrability compared to unassembled versions and efficiently target LDLR in vivo upon systemic administration.Figure optionsDownload high-quality image (200 K)Download as PowerPoint slide
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 12, Issue 5, July 2016, Pages 1241–1251