Human ferritins are emerging platforms for non-toxic protein-based drug delivery, owing to their intrinsic or acquirable targeting abilities to cancer cells and hollow cage structures for drug loading. However, reliable strategies for high-level drug encapsulation within ferritin cavities and prompt cellular drug release are still lacking. Ferritin nanocages were developed with partially opened hydrophobic channels, which provide stable routes for spontaneous and highly accumulated loading of Fe -conjugated drugs as well as pH-responsive rapid drug release at endoplasmic pH. Multiple cancer-related compounds, such as doxorubicin, curcumin, and quercetin, were actively and heavily loaded onto the prepared nicked ferritin. Drugs on these minimally modified ferritins were effectively delivered inside cancer cells with high toxicity.
Scheme 1. Representation of engineering 4-fold channel-nicked human ferritin nanocages. a) Structural representation of human heavy-chain ferritin (HF), E-helix-truncated HF (F160), and nicked ferritin. b) Active drug encapsulationa nd pH-responsive drug release by Nicked-HF.
Protein cages are attractive building blocks to build high order materials such as 3D cage lattices, which offer accurately ordered bio-templates. However, controlling the size or valency of these cage-to-cage...
Human ferritin has been heavily investigated as a protein-based drug deliver agent, due to its unique hollow cage structure for drug loading and an intrinsic tumor targeting function. However, facile strategies for high-level drug loading and controlled release have not been established, which hampered the use of ferritin as an in vivo delivery platform. We examined active drug uptake and release patterns of various flopped ferritin variants, which use fourfold channels as a route for drug uptake. A flopped channel pore structure was adjusted by diverse mutations around the helix-connecting loop of the channel. Active loading and release of anti-cancer drug doxorubicin for these ferritin variants were quantitatively monitored. Drug-loading ability and spontaneous release degree were both enhanced by channel flopping and a pore size increase. The results could lay a stepping stone for further understanding of drug loading via fourfold ferritin channels.
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