Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 8, Issue 5, Pages 647-654Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2011.08.007
Keywords
Drug delivery; Nanotechnology; Endocytosis; Intracellular distribution
Funding
- Canadian Institutes of Health Research (CIHR) [MOP-13270, MOP-42546]
- Ministry of Research and Innovation of Ontario
- Uehara Memorial Foundation
- International Society of Heart and Lung Transplantation
- Grants-in-Aid for Scientific Research [22591464, 22791295] Funding Source: KAKEN
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A special class of self-assembling peptide (EAK16-II) has been found to stabilize the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this study, the mechanism of such peptide-EPT complexes to enhance cellular delivery and anticancer activity was evaluated. Results revealed that EAK16-II can form nanoparticles with EPT, having an average size of similar to 100 nm. This nanoformulation had cytotoxicity to human lung carcinoma A549 cells that was comparable to EPT dissolved in dimethyl sulfoxide. It enhanced EPT uptake drastically when compared to the microformulation. Such enhanced uptake was significantly reduced by inhibitors specifically for the caveolae-dependent pathway. We also found both protonated and neutral forms of EPT present in the cells. Interestingly, both were found in the cytoplasm, co-localized with LysoTracker, whereas only protonated EPT was seen in the nucleus. The promising therapeutic efficacy, specific delivery pathway, and intracellular distribution pattern discovered in this work may help further develop EPT as a nanoformulation for clinical applications.
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