Abstract
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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