Cargo loading within ferritin nanocages in preparation for tumor-targeted delivery

Zhang, Jianlin; Cheng, Dengfeng; He, Jianxun; Hong, Juanji; Yuan, Chang; Liang, Minmin

doi:10.1038/s41596-021-00602-5

Cited by 64 publications

(62 citation statements)

References 96 publications

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“…We developed an iron oxide nanoparticle preparation method within human HFn nanocage that is capable of precisely adjusting the formed nanocores within the cavity of HFn (Figure ). , We demonstrated that the loaded Fe 2+ through the hydrophilic threefold channel on the surface of the human HFn nanocage could be selectively oxidized by precisely dosed H 2 O 2 in an oxygen-free reaction atmosphere to form different sizes of iron oxide nanocores within the HFn nanocage. During this process, Fe 2+ entry and selective oxidation within ferritins are mainly induced by two active sites, acidic residues within the threefold channel and ferroxidase sites, which are distributed throughout the ferritin nanocages.…”

Section: Methods and Mechanisms For Cargo Loading And Releasementioning

confidence: 99%

“…We further successfully prepared Co 3 O 4 and MnO 2 NPs with the controllable size and high uniformity within the human HFn nanocage by adjusting the dosing speed and duration of the added metal ions and H 2 O 2 . To date, the controllable synthesis of inorganic NPs within HoSF, HFt, and other natural and recombinant mammalian ferritins has been successively reported (Table ).…”

Section: Methods and Mechanisms For Cargo Loading And Releasementioning

confidence: 99%

“…31 We further successfully prepared Co 3 O 4 and MnO 2 NPs with the controllable size and high uniformity within the human HFn nanocage by adjusting the dosing speed and duration of the added metal ions and H 2 O 2 . 30 To date, the controllable synthesis of inorganic NPs within HoSF, HFt, and other natural and recombinant mammalian ferritins has been successively reported (Table 1). The combination of the ion entry channels, oxidoreductase catalytic sites, and nucleation centers of ferritin nanocages makes them favorable reaction vessels for the synthesis of highly crystalline and uniform inorganic NPs.…”

Section: Inorganic Nanoparticle Synthesis Within the Ferritin Nanocagementioning

confidence: 99%

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Ferritin: A Multifunctional Nanoplatform for Biological Detection, Imaging Diagnosis, and Drug Delivery

et al. 2021

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Metrics & MoreArticle Recommendations CONSPECTUS: Ferritins are spherical iron storage proteins within cells that are composed of a combination of 24 subunits of two types, heavy-chain ferritin (HFn) and light-chain ferritin (LFn). They autoassemble naturally into a spherical hollow nanocage with an outer diameter of 12 nm and an interior cavity that is 8 nm in diameter. In recent years, with the constantly emerging safety issues and the concerns about unfavorable uniformity and indefinite in vivo behavior of traditional nanomedicines, the characteristics of native ferritin nanocages, such as the unique nanocage structure, excellent safety profile, and definite in vivo behavior, make ferritin-based formulations uniquely attractive for nanomedicine development. To date, a variety of cargo molecules, including therapeutic drugs (e.g., cisplatin, carboplatin, paclitaxel, curcumin, atropine, quercetin, gefitinib, daunomycin, epirubicin, doxorubicin, etc.), imaging agents (e.g., fluorescence dyes, radioisotopes, and MRI contrast agents), nucleic acids (e.g., siRNA and miRNA), and metal nanoparticles (e.g., Fe 3 O 4 , CeO 2 , AuPd, CuS, CoPt, FeCo, Ag, etc.) have been loaded into the interior cavity of ferritin nanocages for a broad range of biomedical applications from in vitro biosensing to targeted delivery of cargo molecules in living systems with the aid of modified targeting ligands either genetically or chemically. We reported that human HFn could selectively deliver a large amount of cargo into tumors in vivo via transferrin receptor 1 (TfR1)-mediated tumor-cell-specific targeting followed by rapid internalization. By the use of the intrinsic tumor-targeting property and unique nanocage structure of human HFn, a broad variety of cargo-loaded HFn formulations have been developed for biological analysis, imaging diagnosis, and medicine development. In view of the intrinsic tumor-targeting property, unique nanocage structure, lack of immunogenicity, and definite in vivo behavior, human HFn holds promise to promote therapeutic drugs, diagnostic imaging agents, and targeting moieties into multifunctional nanomedicines.Since the report of the intrinsic tumor-targeting property of human HFn, we have extensively explored human HFn as an ideal nanocarrier for tumor-targeted delivery of anticancer drugs, MRI contrast agents, inorganic nanoparticles, and radioisotopes. In particular, by the use of genetic tools, we also have genetically engineered human HFn nanocages to recognize a broader range of disease biomarkers. In this Account, we systematically review human ferritins from characterizing their tumor-binding property and understanding their mechanism and kinetics for cargo loading to exploring their biomedical applications. We finally discuss the prospect of ferritin-based formulations to become next-generation nanomedicines. We expect that ferritin formulations with unique physicochemical characteristics and intrinsic tumor-targeting property will attract broad interest in fundamental drug research and offer new op...

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Section: Methods and Mechanisms For Cargo Loading And Releasementioning

confidence: 99%

Section: Methods and Mechanisms For Cargo Loading And Releasementioning

confidence: 99%

Section: Inorganic Nanoparticle Synthesis Within the Ferritin Nanocagementioning

confidence: 99%

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Ferritin: A Multifunctional Nanoplatform for Biological Detection, Imaging Diagnosis, and Drug Delivery

et al. 2021

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“…S3 and S4†). 8,34,35 As Ru1 and Ru2 are highly hydrophilic and stable even at pH 12, 31,33 they were incubated in the presence of HuHf during the disassembly process at different molar ratios (20–200 fold with respect to the protein). In order to remove the excess of Ru1 or Ru2 , i.e.…”

Section: Resultsmentioning

confidence: 99%

Ferritin nanocomposites for the selective delivery of photosensitizing ruthenium-polypyridyl compounds to cancer cells

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Ciambellotti

Giacomazzo

et al. 2022

Inorg. Chem. Front.

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“…We take doxorubicin as an example to illustrate how DNA-based NPs deliver chemotherapeutic drugs. At present, DNA-based NPs of various shapes have been reported for the delivery of doxorubicin by virtue of the drug-embedding properties, covering RCA-based nanostructures ( Zhao et al, 2018 ), DNA tetrahedra ( Zhang J. et al, 2021 ), dendritic DNA nanostructures ( Li et al, 2020 ), and nanostructures based on DNA origami technology ( Liu J. et al, 2018 ), in which tubular and triangular DNA nanocarriers based on DNA origami technology have the characteristics of high drug loading ( Guan et al, 2021 ). Interestingly, DNA-based NPs with specific hydrodynamic dimensions and geometries (triangular DNA origami nanostructures) can passively accumulate in tumor tissues, showing excellent targeting ( Zhang et al, 2014 ; Jiang B. et al, 2019 ).…”

Section: Chemotherapy Nanomedicinementioning

confidence: 99%

Application Perspectives of Nanomedicine in Cancer Treatment

et al. 2022

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Cancer is a disease that seriously threatens human health. Based on the improvement of traditional treatment methods and the development of new treatment modes, the pattern of cancer treatment is constantly being optimized. Nanomedicine plays an important role in these evolving tumor treatment modalities. In this article, we outline the applications of nanomedicine in three important tumor-related fields: chemotherapy, gene therapy, and immunotherapy. According to the current common problems, such as poor targeting of first-line chemotherapy drugs, easy destruction of nucleic acid drugs, and common immune-related adverse events in immunotherapy, we discuss how nanomedicine can be combined with these treatment modalities, provide typical examples, and summarize the advantages brought by the application of nanomedicine.

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Cargo loading within ferritin nanocages in preparation for tumor-targeted delivery

Cited by 64 publications

References 96 publications

Ferritin: A Multifunctional Nanoplatform for Biological Detection, Imaging Diagnosis, and Drug Delivery

Ferritin: A Multifunctional Nanoplatform for Biological Detection, Imaging Diagnosis, and Drug Delivery

Ferritin nanocomposites for the selective delivery of photosensitizing ruthenium-polypyridyl compounds to cancer cells

Application Perspectives of Nanomedicine in Cancer Treatment

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