文献类型：期刊文献

英文题名：Cholesterol-directed nanoparticle assemblies based on single amino acid peptide mutations activate cellular uptake and decrease tumor volume

作者：Li, Shang[1,2];Zou, Rongfeng[1,2,5];Tu, Yaoquan[5];Wu, Junchen[1,2,3];Landry, Markita P.[3,4]

机构：[1]East China Univ Sci & Technol, Sch Chem & Mol Engn, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Chem & Mol Engn, Inst Fine Chem, Shanghai 200237, Peoples R China;[3]Univ Calif Berkeley, Dept Chem & Bio Mol Engn, 476 Stanley Hall, Berkeley, CA 94720 USA;[4]Univ Calif Berkeley, Calif Inst Quantitat Biosci Qb3, Berkeley, CA 94720 USA;[5]KTH Royal Inst Technol, Sch Biotechnol, Div Theoret Chem & Biol, SE-10691 Stockholm, Sweden

年份：2017

卷号：8

期号：11

起止页码：7552

外文期刊名：CHEMICAL SCIENCE

收录：;EI(收录号：20174304310485);WOS:【SCI-EXPANDED(收录号:WOS:000413532800031)】；

基金：We thank the NSFC (91529101, 21572057 and 21778017) for financial support. This work was supported by a Burroughs Welcome Fund Career Award at the Scientific Interface (CASI), the Simons Foundation, a BBRF young investigator award, and a Beckman Foundation Young Investigator Award (M. P. L.). R. Z. thanks the China Scholarship Council for financial support.

语种：英文

外文关键词：Drug delivery - Van der Waals forces - Cancer cells - Cell death - Nanoparticles - Cholesterol - Diagnosis - Molecular biology - Amino acids - Diseases - Tumors

摘要：Peptide drugs have been difficult to translate into effective therapies due to their low in vivo stability. Here, we report a strategy to develop peptide-based therapeutic nanoparticles by screening a peptide library differing by single-site amino acid mutations of lysine-modified cholesterol. Certain cholesterol-modified peptides are found to promote and stabilize peptide a-helix formation, resulting in selectively cell-permeable peptides. One cholesterol-modified peptide self-assembles into stable nanoparticles with considerable alpha-helix propensity stabilized by intermolecular van der Waals interactions between inter-peptide cholesterol molecules, and shows 68.3% stability after incubation with serum for 16 h. The nanoparticles in turn interact with cell membrane cholesterols that are disproportionately present in cancer cell membranes, inducing lipid raft-mediated endocytosis and cancer cell death. Our results introduce a strategy to identify peptide nanoparticles that can effectively reduce tumor volumes when administered to in in vivo mice models. Our results also provide a simple platform for developing peptide-based anticancer drugs.