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: Yongzhong Wang, Sijia Yi, Leming Sun, Yujian Huang, Scott C Lenaghan, Mingjun Zhang
• Journal: Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 10 Issue 3 Pg. 445-54 (Mar 2014) ISSN: 1550-7033 [Print] United States
• PMID: 24730240 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibiotics, Antineoplastic
• Drug Carriers
• Nanoconjugates
• Nanotubes, Peptide
• Polyethylene Glycols
• Doxorubicin

Topics

• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Doxorubicin (administration & dosage, pharmacokinetics)
• Drug Carriers (chemistry, pharmacokinetics)
• Drug Evaluation, Preclinical
• Drug Resistance, Neoplasm (drug effects)
• Female
• Humans
• Hydrogen-Ion Concentration
• MCF-7 Cells
• Nanoconjugates (administration & dosage, chemistry)
• Nanotubes, Peptide (chemistry)
• Polyethylene Glycols (chemistry, pharmacokinetics)
• Polymerization
• Tissue Distribution