RESUMO
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 FeII -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.
Assuntos
Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Preparações de Ação Retardada/química , Doxorrubicina/administração & dosagem , Ferritinas/química , Quercetina/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Curcumina/química , Curcumina/farmacocinética , Doxorrubicina/química , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Modelos Moleculares , Quercetina/química , Quercetina/farmacocinéticaRESUMO
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 assemblies is extremely difficult due to highly multivalent and symmetric cage structures. Here, various high order cage assemblies with homogeneous sizes and geometries are constructed by developing an anisotropic ferritin cage with limitedly exposed binding modules, leucine zipper. The anisotropic ferritin is produced as expressed in cells without the need of complex in vitro cage fabrication by careful subunit manipulation. Ferritin cages with limitedly exposed zippers are assembled around a core ferritin with fully exposed opposing zippers, generating homogeneous high order structures, whereas two fully exposed ferritins are assembled into heterogeneous cage aggregates. Diverse fully exposed core cages are prepared by varying the zipper-ferritin fusion geometries and even by using larger cage structures. With these core cages and the anisotropic ferritin, a range of high order cage assemblies with diverse ferritin valencies (3 to over 12) and sizes (over 40 nm) are created. Cell surface binding and internalization of cage structures are greatly varied by assembly sizes, where high order ferritins are clearly more effective than monomeric ferritin.