A Photoactive Carbon‐Monoxide‐Releasing Protein Cage for Dose‐Regulated Delivery in Living Cells

Abstract

Protein cages can serve as bioinorganic molecular templates for functionalizing metal compounds to regulate cellular signaling. We succeeded in developing a photoactive CO-releasing system by constructing a composite of ferritin (Fr) containing manganese-carbonyl complexes. When Arg52 adjacent to Cys48 of Fr is replaced with Cys, the Fr mutant stabilizes the retention of 48 Mn-carbonyl moieties, which can release the CO ligands under light irradiation, although wild-type Fr retains very few Mn moieties. The amount of released CO is regulated by the extent of irradiation. This could reveal an optimized dose for cooperatively activating the nuclear factor κB (NF-κB) in mammalian cells and the tumor necrosis factor α (TNF-α). These results suggest that construction of a CO-releasing protein cage will advance of research in CO biology.

Light responsive metal–organic frameworks as controllable CO-releasing cell culture substrates

“…12 In addition, the payload of CO in photoCORMAs is higher than in their molecular counterparts, and the extent of leached by-products is limited because the metal carbonyl moiety is immobilized in the scaffold. Thus, to date, photoCORMs have been assembled into dendritic structures, 13 covalently immobilized onto the surfaces of nanoparticles, 14–16 protein cages, 17 or organic polymers, 18 trapped in polymer fibers, 19 and mesoporous silica. 20 …”

Gold-based drug encapsulation within a ferritin nanocage: X-ray structure and biological evaluation as a potential anticancer agent of the Auoxo3-loaded protein

“…Ferritin (Ft) nanocage has been used to encapsulate a variety of drugs and 35 biologically active substances [6], including gadolinium contrast agents [7], desferrioxamine B [8], doxorubicin [9], inorganic and magnetite nanoparticles [10][11], β-carotene [12], a few photosensitizers [13], cisplatin and carboplatin [14][15], rhodium [16] and palladium compounds [17], organometallic CO releasing 40 systems containing Ru and Mn [18][19]. Ferritin (Ft) nanocage has been used to encapsulate a variety of drugs and 35 biologically active substances [6], including gadolinium contrast agents [7], desferrioxamine B [8], doxorubicin [9], inorganic and magnetite nanoparticles [10][11], β-carotene [12], a few photosensitizers [13], cisplatin and carboplatin [14][15], rhodium [16] and palladium compounds [17], organometallic CO releasing 40 systems containing Ru and Mn [18][19].…”

Design of Bioinorganic Materials at the Interface of Coordination and Biosupramolecular Chemistry

“…Recently, metal carbonyls have been used as carbon monoxide (CO)‐releasing molecules (CORMs) for both in vitro and in vivo delivery of CO because CO gas can serve as an intracellular signaling molecule (Figure ) . Thus, delivery of carbon monoxide (CO) into living cells is an area of growing interest and can be investigated using protein assemblies that include metal complexes . To prevent rapid decomposition of [Ru(CO) 3 Cl 2 ] 2 (CORM‐2), it was accumulated inside the apo‐Fr cage for delivery of CO to living cells .…”

“…Moreover, Ueno et al. reported the construction of a photoactive carbon monoxide (CO) release system based on a ferritin mutant . Photoactive CO‐releasing molecules (CORMs) have been recognized as candidates for regulation of cell functions when combined with light stimulus .…”