Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells

Palombarini, Federica; Masciarelli, Silvia; Incocciati, Alessio; Liccardo, Francesca; Fabio, Elisa Di; Iazzetti, Antonia; Fabrizi, Giancarlo; Fazi, Francesco; Macone, Alberto; Bonamore, Alessandra; Boffi, Alberto

doi:10.1186/s12951-021-00921-5

Cited by 43 publications

(28 citation statements)

References 56 publications

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“…Dendrimers are radially symmetric branched polymeric macromolecules with a core–shell structure, and multiple chemical species can be attached to the dendrimer surface to realize specific properties. Inspired by the mechanism of encapsulation and release of cargoes in ferritin, dendrimers have been well-studied for therapeutic and diagnostic applications, such as drug delivery, MRI imaging, and photodynamic therapy. , In addition, Palombarini et al also reported that positively charged poly(amidoamine) dendrimers could be loaded into ferritin nanocages to neutralize the negative charges on the inner surface of ferritin cavity, which can largely increase the encapsulation capacity for nucleic acids …”

Section: Methods and Mechanisms For Cargo Loading And Releasementioning

confidence: 99%

“…In addition, some researchers have also introduced positively charged components ( e.g. , Ca 2+ and aminic dendrimers) to neutralize the negative charges of the inner surface of ferritin to achieve encapsulation of nucleic acid molecules. , With regard to release of the payload, it was reported that human HFn is capable of quick nuclear translocation, which enables nuclear DNA-targeted drug delivery . It was also demonstrated that the HFn-mediated nuclear translocation may support the escape of encapsulated siRNA from lysosomal degradation after endocytosis .…”

Section: Applicationsmentioning

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: Applicationsmentioning

confidence: 99%

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

et al. 2021

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“…As a drug carrier, HFn does not cause toxicity and immune rejection reaction in human body [ 21 ]. In addition, HFn has unique self-assembly properties to form nanoparticle [ 22 ]. By changing pH value of solution, protein subunits of HFn undergo mutual transformation between de-polymerization and self-assembly aggregation [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclosporine A loaded brain targeting nanoparticle to treat cerebral ischemia/reperfusion injury in mice

Liu

Cheng

et al. 2022

J Nanobiotechnol

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Background Ischemic stroke is one of the main causes of death and disability in the world. The treatment for ischemic stroke is to restore blood perfusion as soon as possible. However, when ischemic brain tissue is re-perfused by blood, the mitochondrial permeability transition pore (mPTP) in neuron and microglia is excessively opened, resulting in the apoptosis of neuron and nerve inflammation. This aggravates nerve injury. Cyclosporine A (CsA) inhibits the over-opening of mPTP, subsequently reducing the release of ROS and the apoptosis of cerebral ischemia/reperfusion injured neuron and microglia. However, CsA is insoluble in water and present in high concentrations in lymphatic tissue. Herein, cerebral infarction tissue targeted nanoparticle (CsA@HFn) was developed to treat cerebral ischemia/reperfusion injury. Results CsA@HFn efficiently penetrated the blood-brain barrier (BBB) and selectively accumulated in ischemic area, inhibiting the opening of mPTP and ROS production in neuron. This subsequently reduced the apoptosis of neuron and the damage of BBB. Consequently, CsA@HFn significantly reduced the infarct area. Moreover, CsA@HFn inhibited the recruitment of astrocytes and microglia in ischemic region and polarized microglia into M2 type microglia, which subsequently alleviated the nerve inflammation. Conclusions CsA@HFn showed a significant therapeutic effect on cerebral ischemia/reperfusion injury by alleviating the apoptosis of neuron, nerve inflammation and the damage of BBB in ischemic area. CsA@HFn has great potential in the treatment of ischemic stroke. Graphical Abstract

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“…Self-assembled nanocarrier vaccines provide new ideas, such as ferritin, which is a cage protein of nonviral origin [ 24 ]. It can self-assemble into highly ordered 24 [ 25 , 26 ] polymers and form multiple surfaces to display antigenic epitopes [ 27 ], which can greatly improve immunogenicity and enhance the efficacy of the vaccine while having low heterogeneity [ 28 ]. Some scholars have used ferritin in influenza vaccines [ 29 ], achieving good immune effects and universality.…”

Section: Introductionmentioning

confidence: 99%

Self-assembling ferritin nanoparticles coupled with linear sequences from canine distemper virus haemagglutinin protein elicit robust immune responses

Wang

Qiao

et al. 2022

J Nanobiotechnol

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Background Canine distemper virus (CDV), which is highly infectious, has caused outbreaks of varying scales in domestic and wild animals worldwide, so the development of a high-efficiency vaccine has broad application prospects. Currently, the commercial vaccine of CDV is an attenuated vaccine, which has the disadvantages of a complex preparation process, high cost and safety risk. It is necessary to develop a safe and effective CDV vaccine that is easy to produce on a large scale. In this study, sequences of CDV haemagglutinin (HA) from the Yanaka strain were aligned, and three potential linear sequences, termed YaH3, YaH4, and YaH5, were collected. To increase the immunogenicity of the epitopes, ferritin was employed as a self-assembling nanoparticle element. The ferritin-coupled forms were termed YaH3F, YaH4F, and YaH5F, respectively. A full-length HA sequence coupled with ferritin was also constructed as a DNA vaccine to compare the immunogenicity of nanoparticles in prokaryotic expression. Result The self-assembly morphology of the proteins from prokaryotic expression was verified by transmission electron microscopy. All the proteins self-assembled into nanoparticles. The expression of the DNA vaccine YaHF in HEK-293T cells was also confirmed in vitro. After subcutaneous injection of epitope nanoparticles or intramuscular injection of DNA YaHF, all vaccines induced strong serum titres, and long-term potency of antibodies in serum could be detected after 84 days. Strong anti-CDV neutralizing activities were observed in both the YaH4F group and YaHF group. According to antibody typing and cytokine detection, YaH4F can induce both Th1 and Th2 immune responses. The results of flow cytometry detection indicated that compared with the control group, all the immunogens elicited an increase in CD3. Simultaneously, the serum antibodies induced by YaH4F and YaHF could significantly enhance the ADCC effect compared with the control group, indicating that the antibodies in the serum effectively recognized the antigens on the cell surface and induced NK cells to kill infected cells directly. Conclusions YaH4F self-assembling nanoparticle obtained by prokaryotic expression has no less of an immune effect than YaHF, and H4 has great potential to become a key target for the easy and rapid preparation of epitope vaccines. Graphical Abstract

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Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells

Cited by 43 publications

References 56 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

Cyclosporine A loaded brain targeting nanoparticle to treat cerebral ischemia/reperfusion injury in mice

Self-assembling ferritin nanoparticles coupled with linear sequences from canine distemper virus haemagglutinin protein elicit robust immune responses

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