Abstract
In this work, we have exploited the unique properties of a chimeric archaeal-human ferritin to encapsulate, deliver and release cytochrome c and induce apoptosis in a myeloid leukemia cell line. The chimeric protein combines the versatility in 24-meric assembly and cargo incorporation capability of Archaeglobus fulgidus ferritin with specific binding of human H ferritin to CD71, the “heavy duty” carrier responsible for transferrin-iron uptake. Delivery of ferritin-encapsulated cytochrome C to the Acute Promyelocytic Leukemia (APL) NB4 cell line, highly resistant to transfection by conventional methods, was successfully achieved in vitro. The effective liberation of cytochrome C within the cytosolic environment, demonstrated by double fluorescent labelling, induced apoptosis in the cancer cells.
Highlights
Therapeutic proteins are emerging as a new important class of drugs employed to treat some high-incidence human diseases including cancer, metabolic disorders, autoimmune diseases, etc
Human H ferritins are naturally targeted toward TfR1 receptor highly expressed in iron avid, fast replicating, tumor cells[10]
We report cytochrome C delivery to Acute Promyelocytic Leukemia (APL) NB4 cell line by means of a chimeric archeal-human ferritin (HumFt) that combines the unique salt mediated association/ dissociation equilibrium of Archaeoglobus fulgidus ferritin with the human H ferritin ability of recognizing CD71 receptor
Summary
Therapeutic proteins are emerging as a new important class of drugs employed to treat some high-incidence human diseases including cancer, metabolic disorders, autoimmune diseases, etc. All proposed applications rely in the delivery of small therapeutic molecules or metal labels encapsulated within the human H-ferritin homopolymer within a procedure that entails subunit dissociation of the ferritin 24-mer at extreme pH values (10.0) followed by neutralization and subsequent encapsulation of the small molecule of interest Such procedure, is not amenable to the encapsulation of most proteins that display both acid or alkaline folding instability. Cytochrome C is a small protein (104 aminoacids) with distinct basic properties (pI = 10.8) due to the presence of excess positive charges necessary for the interaction with the terminal oxidase in mitochondria as well as with the apoptotic protease activating factor-1 (Apaf-1) in the cytosol[17,18] This last interaction triggers apoptosome assembly and caspase cascade that eventually lead to cell death[19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
