Genetically functionalized ferritin nanoparticles with a high-affinity protein binder for immunoassay and imaging

Kim, Jong-Won; Heu, Woosung; Jeong, Sukyo; Kim, Kwang Ho

doi:10.1016/j.aca.2017.07.060

Cited by 19 publications

(12 citation statements)

References 35 publications

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“…Nevertheless, ferritin nanoparticles are fascinating materials due to their robust chemical and structural stability [ 39 , 40 ]. Furthermore, these nanoparticles with multivalent targeting moieties could improve the binding affinity to targets, resulting in highly sensitive and specific delivery [ 24 ]. Taken together, based on our results, ferritin nanoparticles have a considerable potential for further diagnostic and drug-delivery-related applications, specifically in the context of bone-related diseases.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, this approach is attractive in that the outer surface of ferritin nanoparticles could be chemically or genetically modified with targeting motifs, making the process of targeting more precise. Since the ferritin nanoparticles are composed of 24 subunits and can be genetically modified to expose multiple ligands onto the exterior surface, an eventual improvement in the binding affinity can be expected [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging

Kim

Lee

Park

et al. 2021

IJMS

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Bone homeostasis plays a major role in supporting and protecting various organs as well as a body structure by maintaining the balance of activities of the osteoblasts and osteoclasts. Unbalanced differentiation and functions of these cells result in various skeletal diseases, such as osteoporosis, osteopetrosis, and Paget’s disease. Although various synthetic nanomaterials have been developed for bone imaging and therapy through the chemical conjugation, they are associated with serious drawbacks, including heterogeneity and random orientation, in turn resulting in low efficiency. Here, we report the synthesis of bone-targeting ferritin nanoparticles for bone imaging. Ferritin, which is a globular protein composed of 24 subunits, was employed as a carrier molecule. Bone-targeting peptides that have been reported to specifically bind to osteoblast and hydroxyapatite were genetically fused to the N-terminus of the heavy subunit of human ferritin in such a way that the peptides faced outwards. Ferritin nanoparticles with fused bone-targeting peptides were also conjugated with fluorescent dyes to assess their binding ability using osteoblast imaging and a hydroxyapatite binding assay; the results showed their specific binding with osteoblasts and hydroxyapatite. Using in vivo analysis, a specific fluorescent signal from the lower limb was observed, demonstrating a highly selective affinity of the modified nanoparticles for the bone tissue. These promising results indicate a specific binding ability of the nanoscale targeting system to the bone tissue, which might potentially be used for bone disease therapy in future clinical applications.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging

Kim

Lee

Park

et al. 2021

IJMS

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“…It is likely that the EGFRspecific repebody conjugated to the prodrimers maintains its binding capability for human EGFR ectodomain similar to a free repebody. A protein assembly with multiple valency is expected to provide an enhanced binding capability toward a target mainly through the avidity [30][31][32] . To test this expectation, we measured the binding affinities of the prodrimers functionalized with Tmono carrying the EGFR-specific repebody using surface plasmon resonance (SPR) (Figure 2e).…”

Section: Functionalization Of Prodrimersmentioning

confidence: 99%

Dendrimer-like supramolecular assembly of proteins with a tunable size and valency through stepwise iterative growth

Bae

Kim

Gijeong

et al. 2021

Preprint

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The assembly of proteins in a programmable manner provides insight into the underlying mechanisms of protein self-assembly in nature as well as the creation of novel functional nanomaterials for practical applications. Despite many advances, however, a rational protein assembly with an easy scalability in terms of size and valency remains a challenging task. Here, we present a simple bottom-up approach to the supramolecular protein assembly with a tunable size and valency in a programmable manner. The dendrimer-like protein assembly, called a prodrimer, was constructed using a total of three monomeric proteins: a core and two building-block proteins. The prodrimer generations were grown by a stepwise and alternate addition of a building block using two pairs of orthogonal protein-peptide interactions, leading to a higher-generation prodrimer with a mega-dalton size and multi-valency. The valency of the prodrimers at the periphery was tunable with the generation, enabling a single-step functionalization. A second-generation prodrimer functionalized with a target-specific protein binder showed a three-order of magnitude increase in binding affinity compared to a monomeric counterpart due to the avidity. The prodrimers functionalized with a targeting moiety and a cytotoxic protein cargo exhibited a highly enhanced cellular cytotoxicity, exemplifying their utility as a protein delivery platform. The present approach can be effectively used in the creation of protein architectures with new functions for biotechnological and medical applications.

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“…[26][27][28][29] Moreover, it has been shown that the multimeric directional display improves the binding between the functional peptides and their targets. [30] To improve the sensitivity and positive rate of pSS, we herein developed a nanocage-based capture probe by displaying M3 and α-Fodrin peptides on the surface of ferritin nanocage. Multimeric display of M3/α-Fodrin peptides on the ferritin nanocage significantly enhanced their binding with corresponding antibodies and improved the detecting sensitivity more than tenfold compared with the conventional ELISA method.…”

Section: Introductionmentioning

confidence: 99%

“…[ 26–29 ] Moreover, it has been shown that the multimeric directional display improves the binding between the functional peptides and their targets. [ 30 ]…”

Section: Introductionmentioning

confidence: 99%

Nanocage‐Based Capture‐Detection System for the Clinical Diagnosis of Autoimmune Disease

Zhang

et al. 2021

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The detection of autoantibodies is critical for diagnosis of autoimmune diseases. However, the sensitivity is often limited by the properties of the antigens and the detection systems such as enzyme‐linked immunosorbent assay (ELISA). Here, employing the multidisplay ability of ferritin, a highly sensitive nanocage‐based capture‐detection system is designed, of which the sensitivity is 100–1000‐fold higher than that of conventional ELISA methods. The capture nanocages are constructed by displaying the primary Sjögren's syndrome (pSS)‐related antigenic peptides on ferritin nanocage, which present epitopes effectively and high affinity, leading to tenfold higher capture capability for autoantibodies. Human IgG Fc‐binding peptides are also engineered on ferritin nanocage, which enable high binding affinity and efficient horseradish peroxidase (HRP)‐labeling. Compared with commercial HRP‐conjugated anti‐human IgG antibody, the nanocage‐based detecting probe exhibited more than tenfold increased sensitivity. Autoantibodies are then examined in 91 sera from patients with pSS, 51 from rheumatoid arthritis, 54 from systemic lupus erythematosus, and 55 from healthy individuals by using the nanocage‐based ELISA. The results indicate that the nanocage‐based capture‐detection system is an effective detection platform and provide a novel and more sensitive method for the diagnosis of autoimmune diseases.

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Genetically functionalized ferritin nanoparticles with a high-affinity protein binder for immunoassay and imaging

Cited by 19 publications

References 35 publications

Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging

Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging

Dendrimer-like supramolecular assembly of proteins with a tunable size and valency through stepwise iterative growth

Nanocage‐Based Capture‐Detection System for the Clinical Diagnosis of Autoimmune Disease

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