H‐Chain Ferritin: A Natural Nuclei Targeting and Bioactive Delivery Nanovector

Abstract

Nuclear translocation of human H‐chain in its intact cage‐like structure without any additional modifications enables a rapid nuclear delivery of an encapsulated anticancer drug (doxorubicin). This reduces the doses of drugs simultaneously bypassing the cellular multidrug resistance. Apoferritin exhibits synergistic effects through attenuating drug‐induced dysregulation of the cellular iron. Tests on cerebellar organotypic cultures show the natural cell selectivity and drug accumulation in brain tissue.

Nanometronomic treatment of 4T1 breast cancer with nanocaged doxorubicin prevents drug resistance and circumvents cardiotoxicity

“…Treatment with 0.01 μM HFn-DOX caused pronounced apoptosis and necrosis induction and double strand breaks in contrast to DOX (Figure 1F). It can be assumed that the increase in cytotoxicity of HFn-DOX resides in the efficiency of HFn in promoting DOX nuclear translocation (Figure 1G), as already described for different tumor cell lines [25, 26]. Quantitative fluorescence analysis of confocal images gave a nuclear DOX concentration of 15.2 and 9-fold higher than that detected in cultures treated with DOX at 0.1 and 1 μM, respectively (Supplementary Figure 2).…”

“…HFn-DOX dose was set at 1.24 mg kg −1 DOX, about 1/7 of the average MTD dosage administered in 4T1 murine BC [26]. This tumor model was selected for its aggressiveness and spontaneous tendency to spread to multiple metastatic sites after orthotopic injection of luciferase-tagged cells.…”

Encapsulation of the Dinuclear Trithiolato‐Bridged Arene Ruthenium Complex Diruthenium‐1 in an Apoferritin Nanocage: Structure and Cytotoxicity

“…Apoferritin (AFt) has been widely used as a protein cage to entrap metal‐based drugs, as it can be reversibly dissociated and reassembled upon pH variation. Adducts formed upon encapsulation of drugs within AFt cages have the advantage of enhanced selectivity for tumor cells, because H‐ and L‐chains as well as H/L heteropolymers can be recognized by surface receptors that are overexpressed by various tumor cell lines …”

“…Apoferritin (AFt) has been widely used as ap rotein cage to entrapm etal-based drugs, as it can be reversibly dissociated and reassembledu pon pH variation.A dducts formedu pon encapsulation of drugs within AFt cages have the advantage of enhanced selectivity for tumor cells, [6] because H-and L-chains as well as H/Lheteropolymers can be recognized by surface receptors that are overexpressed by various tumor cell lines. [7,8] Recently,c isplatin, [9][10][11][12][13] carboplatin, [11][12][13][14] ab imetallic cytotoxic gold-platinum compound (4PF 6 ), [15] and cytotoxic gold(III) compounds, namely Auoxo3 ([Au 2 (bipy Me ) 2 (m-O) 2 ][PF 6 ] 2 ,w here bipy Me = 6-methyl-2,2'-bipyridine), [6] Auoxo4 ([Au 2 (bipy nP ) 2 (m-O) 2 ] [PF 6 ] 2 ,w here bipy nP = 6-neopentyl-2,2'-bipyridine) and Au 2 phen ([Au 2 (phen 2 Me ) 2 (m-O) 2 ][PF 6 ] 2 ,w here phen 2 Me = 2,9-dimethyl-1,10phenanthroline), [16] have been successfully encapsulatedw ithin the horse spleen AFt nanocage. X-ray diffraction analysis showst hat cisplatin and carboplatin bind the AFt chain close to the imidazole rings of His132, and His132a nd His49, respectively.…”

LC–MS/MS method development for quantification of doxorubicin and its metabolite 13‐hydroxy doxorubicin in mice biological matrices: Application to a pharmaco‐delivery study

“…While CAELYX mediates the DOX tumor delivery taking advantage of the enhanced permeability and retention effect, HFer-DOX triggered a tumor-targeted nuclear delivery of drug(Barenholz, 2012;Bellini et al, 2014;Zhang et al, 2015). In particular, analytes are stable in biomatrices for 15 h at room temperature, five freeze-thaw cycles and for 3 days at room temperature (processed samples).…”