Integrin-targeting ferritin for drug delivery and tumor imaging
Journal
FASEB JOURNAL
Journal Volume
34
Journal Issue
1-1
ISSN
1530-6860
0892-6638
Date Issued
2020-04
Author(s)
Abstract
Various potent chemotherapeutic drugs have been developed over decades. Doxorubicin, the lead compound of the anthracycline family, has been applied clinically in a wide range of malignancies including leukemia, lymphomas, myeloma, breast cancer, lung cancer and sarcoma etc. Despite its profound therapeutic efficacy, this chemotherapeutic drug causes numerous side toxicity effects. One main side effect is cardiotoxicity. To eliminate the side effect of this conventional chemotherapeutic drug, targeted delivery of chemotherapeutic drugs to tumor cells is being investigated. This concept can be achieved using nano-scaled drug-containing particles, which are called nanoparticles. Many promising nanoparticles with various materials have been developed, such as liposomes, micelles, and carbon nanotubes. However, biocompatibility and metabolism issues related to these nanoparticles have limited their clinical applications. Hence, various nanoparticles have been fabricated to improve above disadvantages. Ferritin, consisting of 24 subunits, could self-assemble into a shell-like sphere and which make ferritin a suitable drug-carrier. Moreover, with precisely assembled nanoscale shape, high safety and biocompatibility, ferritin has the potential for in vivo imaging and therapeutic purpose.
Integrin α2β1 is a major collagen receptor that highly expresses on various tumor cells such as prostate, lung, and colorectal cancer cells. In this study, we have constructed integrin-targeted ferritin which expresses integrin α2β1-targeting peptide on the ferritin surface to specifically target cell lines with high-expression of integrin α2β1. Our results indicated that the integrin-targeted ferritin showed higher doxorubicin loading efficiency and yield than unmodified ferritin. Moreover, flow cytometry analysis showed that integrin-targeted ferritin had better binding ability to U-87 MG and PC3, cell lines with high integrin α2β1 expression, than unmodified ferritin. Furthermore, in cell cytotoxicity assay, doxorubicin encapsulated within integrin-targeted ferritin showed higher cytotoxicity effects than doxorubicin encapsulated within unmodified ferritin and free doxorubicin in U-87 MG and PC3 cells. All of our results support that integrin-targeted ferritin has the potential to be a novel anticancer nanomedicine.
SDGs
Publisher
John Wiley & Sons
Type
meeting abstract