Abstract:
:In vivo peptide inhibition of tumor suppressor p53 binding to the protein MDM2 is hampered by inefficient delivery of the peptide. Our approach to couple a hydrophobic lipid-like tail on the inhibitory peptide p53(14-29) allowed its intracellular delivery in vitro, in a panel of different cell lines. The constructed chimeric molecules, termed peptide amphiphiles, further self-assembled into supramolecular structures, identified as elongated wormlike micelles. Internalization of peptides occurred following micelle disassembly, partly via clathrin-mediated endocytosis of monomers. Incubation of SJSA-1 cells in hypertonic culture media, aimed to disrupt endocytic vesicles, resulted in peptide amphiphile-mediated cell death. Our results provide the basis for the construction of novel therapeutic supramolecular nanoparticles and suggest hydrophobic modification of peptides as a promising strategy for enhancing delivery of impermeable peptides.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Missirlis D,Krogstad DV,Tirrell Mdoi
10.1021/mp100193hsubject
Has Abstractpub_date
2010-12-06 00:00:00pages
2173-84issue
6eissn
1543-8384issn
1543-8392journal_volume
7pub_type
杂志文章abstract::The primary cause of mortality for glioblastoma (GBM) is local tumor recurrence following standard-of-care therapies, including surgical resection. With most tumors recurring near the site of surgical resection, local delivery of chemotherapy at the time of surgery is a promising strategy. Herein drug-loaded polymer s...
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pub_type: 临床试验,杂志文章
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