Design and characterization of a multifunctional pH-triggered peptide C8 for selective anticancer activity
| Autor: | Tao Zheng, Heiko Heerklotz, Wen Xu, Yongfang Yuan, Ping Kai Ouyang, Lei Zhang, Mej Mikko Karttunen, Danyang Zhao, Yong Ding, Jason Li, W. F. Drew Bennett, Helen Y. Fan, Dafeng Chu, Sheng Lu, Pu Chen, Yan Wu |
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| Přispěvatelé: | Signal Processing Systems, Center for Analysis, Scientific Computing & Appl. |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Biomedical Engineering
Nanofibers Pharmaceutical Science Peptide Antineoplastic Agents SDG 3 – Goede gezondheid en welzijn Biomaterials Mice Drug Delivery Systems SDG 3 - Good Health and Well-being Cell Line Tumor Animals Humans Histidine Ellipticines Cytotoxicity chemistry.chemical_classification Liposome Drug Carriers Cell specificity Hydrogen-Ion Concentration Amino acid Nanostructures Membrane chemistry Biochemistry Cancer cell Drug delivery Liposomes PH-responsiveness Biophysics NIH 3T3 Cells Drug carrier Peptides Anticancer peptides |
| Zdroj: | Advanced Healthcare Materials, 4(17), 2709-2718. Wiley |
| ISSN: | 2192-2640 |
| DOI: | 10.1002/adhm.201500636 |
| Popis: | Most drug delivery systems have been developed for efficient delivery to tumor sites via targeting and on-demand strategies, but the carriers rarely execute synergistic therapeutic actions. In this work, C8, a cationic, pH-triggered anticancer peptide, is developed by incorporating histidine-mediated pH-sensitivity, amphipathic helix, and amino acid pairing self-assembly design. We designed C8 to function as a pH-responsive nanostructure whose cytotoxicity can be switched on and off by its self-assembly: Noncytotoxic β-sheet fibers at high pH with neutral histidines, and positively charged monomers with membrane lytic activity at low pH. The selective activity of C8, tested for three different cancer cell lines and two noncancerous cell lines, is shown. Based on liposome leakage assays and multiscale computer simulations, its physical mechanisms of pore-forming action and selectivity are proposed, which originate from differences in the lipid composition of the cellular membrane and changes in hydrogen bonding. C8 is then investigated for its potential as a drug carrier. C8 forms a nanocomplex with ellipticine, a nonselective model anticancer drug. It selectively targets cancer cells in a pH-responsive manner, demonstrating enhanced efficacy and selectivity. This study provides a novel powerful strategy for the design and development of multifunctional self-assembling peptides for therapeutic and drug delivery applications. |
| Databáze: | OpenAIRE |
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