Journal
MACROMOLECULAR RAPID COMMUNICATIONS
Volume 38, Issue 21, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/marc.201700490
Keywords
controlled release; dendritic peptides; MDR tumor therapy; nuclear localization; self-assembly
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Funding
- National Natural Science Foundation of China [51373128, 51573142]
- Educational Commission of Hubei Province of China [Q20171509]
- Wuhan Institute of Technology [K201701]
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In recent decades, diverse drug delivery systems (DDS) constructed by self-assembly of dendritic peptides have shown advantages and improvable potential for cancer treatment. Here, an arginine-enriched dendritic amphiphilic chimeric peptide CRRK(RRCG(Fmoc))(2) containing multiple thiol groups is programmed to form drug-loaded nano-micelles by self-assembly. With a rational design, the branched hydrophobic groups (Fmoc) of the peptides provide a strong hydrophobic force to prevent the drug from premature release, and the reduction-sensitive disulfide linkages formed between contiguous peptides can control drug release under reducing stimulation. As expected, specific to multidrug resistance (MDR) tumor cells, the arginine-enriched peptide/drug (PD) nano-micelles show accurate nuclear localization ability to prevent the drug being pumped by P-glycoprotein (P-gp) in vitro, as well as exhibiting satisfactory efficacy for MDR tumor treatment in vivo. This design successfully realizes stimuli-responsive drug release aimed at MDR tumor cells via an ingenious sequence arrangement.
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