Doxorubicin-Loaded Cyclic Peptide Nanotube Bundles Overcome Chemoresistance in Breast Cancer Cells

The purpose of this study was to design and fabricate a new cyclic peptide-based nanotube (CPNT) and to explore its potential application in cancer therapy. For such a purpose, the CPNT bundles with a diameter of ∼10 nm and a length of ∼50–80 nm, self-assembled in a micro-scaled aggregate, were first prepared using a glutamic acid and a cysteine residue-containing cyclic octapeptide. In order to explore the potential application of these supramolecular structures, the CPNTs were loaded with doxorubicin (DOX), and further modified using polyethylene glycol (PEG). The PEG-modified DOX-loaded CPNTs, showing high drug encapsulation ratio, were nano-scaled dispersions with a diameter of ∼50 nm and a length of ∼200–300 nm. More importantly, compared to free DOX, the PEG-modified DOX-loaded CPNT bundles demonstrated higher cytotoxicity, increased DOX uptake and altered intracellular distribution of DOX in human breast cancer MCF-7/ADR cells in vitro. In addition, an enhanced inhibition of P-gp activity was observed in MCF-7/ADR cells by the PEG-modified DOX-loaded CPNT bundles, which shows their potential to overcome the multidrug resistance in tumor therapy. These findings indicate that using cyclic peptide-based supramolecular structures as nanocarriers is a feasible and a potential solution for drug delivery to resistant tumor cells.