Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

Mosca, Luciana; Falvo, Elisabetta; Ceci, Pierpaolo; Poser, Elena; Genovese, Ilaria; Guarguaglini, Giulia; Colotti, Gianni

doi:10.3390/app7010101

Cited by 15 publications

(10 citation statements)

References 56 publications

(44 reference statements)

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“…Masuda et al did the heating of lysate at 60 • C for 10 min and then AS precipitation, prior to IEC and SEC for HFn purification [6]. A fourstep purification pathway comprising 70 • C lysate heating, Hitrap Q high performance IEC, ultra-centrifugation and AS precipitation was adopted in two previous studies [7,8]. In other research, lysate heating followed by AS precipitation, plus DNase and RNase treatment and SEC were performed to remove HCPs and nucleic acid [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Development of purification process for dual‐function recombinant human heavy‐chain ferritin by the investigation of genetic modification impact on conformation

Yin

Zhang

Jun

et al. 2021

Engineering in Life Sciences

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Ferritin is a promising drug delivery platform and has been functionalized through genetic modifications. This work has designed and expressed a dualfunctional engineered human heavy-chain ferritin (HFn) with the inserted functional peptide PAS and RGDK to extend half-life and improve tumor targeted drug delivery. A facile and cost-effective two-step purification pathway for recombinant HFn was developed. The genetic modification was found to affect HFn conformation, and therefore varied the purification performance. Heat-acid precipitation followed by butyl fast flow hydrophobic interaction chromatography (HIC) has been developed to purify HFn and modified HFns. Nucleic acid removal reached above 99.8% for HFn and modified HFns. However, HFn purity reached above 95% and recovery yield (overall) above 90%, compared with modified HFns purity above 82% and recovery yield (overall) above 58%. It is interesting to find that the inserted functional peptides significantly changed the molecule conformation, where a putative turnover of the E-helix with the inserted functional peptides formed a "flop" conformation, in contrast with the "flip" conformation of HFn. It could be the cause of fragile stability of modified HFns, and therefore less tolerant to heat and acid condition, observed by the lower recovery yield in heat-acid precipitation.

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Section: Introductionmentioning

confidence: 99%

Development of purification process for dual‐function recombinant human heavy‐chain ferritin by the investigation of genetic modification impact on conformation

Yin

Zhang

Jun

et al. 2021

Engineering in Life Sciences

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“…Protein-cage molecules based on the H-chain of human ferritin (HFt) have been recently attracting growing interest in the field of cancer drug delivery, due to their excellent biocompatibility, selectivity for cancer over normal cells, binding to a large number of different human tumors and ability to encapsulate in their internal cavity high amounts (20–120 molecules) of different drug classes [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The cage-like shape is due to the fact that HFt is a multimeric protein consisting of 24 identical subunits that self-assembly into a symmetric hollow sphere, with external and internal diameters of 12 and 8 nm, respectively [ 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy

et al. 2020

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Gastrointestinal tumors, including pancreatic and colorectal cancers, represent one of the greatest public health issues worldwide, leading to a million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different types of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors.

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“…Ferritin is itself a catalytic bionanoparticle and nanocarrier, a safer choice, when engineered or appropriately distributed in a biological system. Mosca et al, (2017) studied the ability of ferritin to bind and deliver metals and metalbased drugs to human neuroblastoma SH-SY5Y cells. They used heavy chain (H) ferritin-based metal-containing nanocarriers used for the delivery of toxic molecules to brain cells, Iron-containing nanocarriers have a proliferative effect and ferritins can be used for the delivery of toxic molecules to brain tumors.…”

Section: Applicationmentioning

confidence: 99%