title: Doxorubicin-loaded cyclic peptide nanotube bundles overcome chemoresistance in breast cancer cells.
abstract: 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.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Sijia
authors.initials: S
authors.lastname: Yi
authors.forename: Leming
authors.initials: L
authors.lastname: Sun
authors.forename: Yujian
authors.initials: Y
authors.lastname: Huang
authors.forename: Scott C
authors.initials: SC
authors.lastname: Lenaghan
authors.forename: Mingjun
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry; D045333:Nanotubes, Peptide / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D058105:Polymerization; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D058726:Nanoconjugates; D045333:Nanotubes, Peptide; D011092:Polyethylene Glycols; D004317:Doxorubicin