pH triggered re-assembly of nanosphere to nanofiber: The role of peptide conformational change for enhanced cancer therapy

Journal of Controlled Release : Official Journal of the Controlled Release Society
Peiqing LiangChangyun Quan

Abstract

pH-triggered conformational change and subsequent re-assembly of nanostructures provide a new strategy in nanomedicine for controlled drug release and enhanced therapy. Here, we reported the development of a novel pH-responsive nano-assembly as a drug carrier from peptide amphiphile (PA) consisting of mimicking peptide and stearic acid moieties. The mimicking peptide is a basic 17-amino acid peptide derived from antennapedia homeodomain, and undergoes a conformational transition of the secondary structure from β-sheet at pH7.4 to α-helix at pH5.0. Such transition therefore leads to simultaneous evolution of the self-assembled structure of PA from nanosphere to nanofiber, promotes assemblies retention and then release drugs in the cytoplasm of tumor cell. In vitro studies showed that the doxorubicin (Dox)-loaded PA nanoparticle (PA@Dox) could be uptaken efficiently by the cell due to the membrane penetrating capability of the mimicking peptide and subsequently the released Dox further induce apoptosis of murine colon carcinoma CT26 (MCCC) cell. In a mouse xenograft model of MCCC, administration of PA@Dox via lateral tail vein injection could remarkably retard the tumor growth. The overall results suggested that the PA-based nano...Continue Reading

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