Ferritin variants: inspirations for rationally designing protein nanocarriers

Jin, Yiliang; He, Jianxun; Fan, Kelong; Yan, Xiyun

doi:10.1039/c9nr03823j

Cited by 46 publications

(38 citation statements)

References 81 publications

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“…[ 26 ] In addition, ferritin nanocages can be robustly produced by biological system (e.g., Escherichia coli ( E. coli ) system) with uniform size and unique structure, and can be modified with additional targeting motifs through genetic engineering, making it a promising candidate for tumor‐targeting drug delivery system. [ 27,28 ] However, limited by the hydrophilic nature of soluble protein, it has fallen short of achieving the objective to effectively load hydrophobic drugs, which are usually eliminated rapidly from the body and have low bioavailability. [ 29 ] Upload of both hydrophilic and hydrophobic drugs on one protein nanocarrier posts additionally challenges.…”

Section: Introductionmentioning

confidence: 99%

Bioengineered Dual‐Targeting Protein Nanocage for Stereoscopical Loading of Synergistic Hydrophilic/Hydrophobic Drugs to Enhance Anticancer Efficacy

Wang

Zhang

et al. 2021

Adv Funct Materials

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A biocompatible and modifiable protein nanocarrier is a promising candidate for tumor targeted drug delivery. However, it is challenging to effectively load hydrophobic drugs, not to mention to upload both hydrophilic and hydrophobic drugs on one protein nanocarrier. Here, an amphiphilic multi-drug loading protein nanocage (Am-PNCage) is presented which is generated by replacing the fifth helix of human H-ferritin (HFn) subunit with a functional motif composed of hydrophobic-hydrophilic-RGD peptides. The Am-PNCage possesses a dual targeting property resulting from the intrinsic CD71 targeting ability of HFn and the integrin α vβ3 targeting ability of displayed RGD peptides. Through the hydrophilic drug entry channel in the protein nanocage and hydrophobic peptides displayed on the outer surface, amphiphilic epirubicin (132)/camptothecin (50) are stereoscopically loaded into the inner cavity/outer protein shell, respectively, for one Am-PNCage, exhibiting cascade drug release pattern. The dual-targeted Am-PNCage promotes the loaded drugs penetrating various 3D tumor models in vitro, as well as traversing the brain blood barrier and accumulating in brain tumors in vivo. Moreover, the drug loaded Am-PNCage shows reduced side effects and significantly enhances synergistic efficacy against brain tumor, metastatic liver cancers, and drug resistant breast tumor. Thus, the Am-PNCage represents a novel promising protein nanocarrier for targeted combination chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Bioengineered Dual‐Targeting Protein Nanocage for Stereoscopical Loading of Synergistic Hydrophilic/Hydrophobic Drugs to Enhance Anticancer Efficacy

Wang

Zhang

et al. 2021

Adv Funct Materials

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“…[68] It is also reported that genetic manipulation can be firmly tuned for functional ferritin nanocages which expand biomedical applications of ferritin. [69] The basic difference between the protein-based nanocage as cargo for intracellular delivery and that of the MOF-based protein carriers is that EMP NPs not only protect the protein cargoes but also indulge in the phagocyte-dependent clearance of cargoes by selectively targeting the tumor site. [70,71] In general, when MOFs act as immobilizers and storage of functional proteins, they stimulate from the mesoporous structure that allows high protein loadings, including a framework architecture for providing both chemical and thermal stabilities for encapsulated proteins.…”

Section: Protein Nanocages Versus Mof-biomolecule Npsmentioning

confidence: 99%

Exoskeleton for Biofunctionality Protection of Enzymes and Proteins for Intracellular Delivery

Dutta

2020

Advanced NanoBiomed Research

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Driven by the challenges to protect and restore biofunctionality of enzymes and proteins due to fluctuation of temperature, pH, and solvents, desired tolerances against the intracellular microenvironment can be gained via sheltering enzyme and proteins into nanoscale cages of exoskeleton, one of which involves confinement into the pore and channels of metal–organic frameworks (MOFs). While confining biomolecules, such framework exoskeleton and nanoscale cages should drive the enzyme embedding process and induce the formation of the resulting biocomposite suitable for intracellular delivery for therapeutic applications. Translational challenges faced by framework materials such as ZIF‐8 exoskeleton along with few more MOFs for armoring biofunctionality modulation of enzymes and proteins for intracellular delivery efficiency are highlighted. Herein, enzyme embedding patterns, encapsulation of oxidase enzymes, hybrid protein–MOFs, protected protein delivery, and mechanism of biofunctionality protection are discussed. Furthermore, an attempt is made to highlight the scope of exoskeleton biocomposites.

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“…The outer and inner diameters of ferritin cages are 12 and 8 nm, respectively, and they also carry a central cavity to store iron [16]. One of the reasons ferritin is so useful for biological applications is because the surfaces of ferritin, including the inner, outer, and inter-subunit interfaces, are amenable to different types of modifications [20,21].…”

Section: Introductionmentioning

confidence: 99%

Multivalent Display of SARS-CoV-2 Spike (RBD Domain) of COVID-19 to Nanomaterial, Protein Ferritin Nanocages

et al. 2021

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SARS-CoV-2, or COVID-19, has a devastating effect on our society, both in terms of quality of life and death rates; hence, there is an urgent need for developing safe and effective therapeutics against SARS-CoV-2. The most promising strategy to fight against this deadly virus is to develop an effective vaccine. Internalization of SARS-CoV-2 into the human host cell mainly occurs through the binding of the coronavirus spike protein (a trimeric surface glycoprotein) to the human angiotensin-converting enzyme 2 (ACE2) receptor. The spike-ACE2 protein–protein interaction is mediated through the receptor-binding domain (RBD) of the spike protein. Mutations in the spike RBD can significantly alter interactions with the ACE2 host receptor. Due to its important role in virus transmission, the spike RBD is considered to be one of the key molecular targets for vaccine development. In this study, a spike RBD-based subunit vaccine was designed by utilizing a ferritin protein nanocage as a scaffold. Several fusion protein constructs were designed in silico by connecting the spike RBD via a synthetic linker (different sizes) to different ferritin subunits (H-ferritin and L-ferritin). The stability and the dynamics of the engineered nanocage constructs were tested by extensive molecular dynamics simulation (MDS). Based on our MDS analysis, a five amino acid-based short linker (S-Linker) was the most effective for displaying the spike RBD over the surface of ferritin. The behavior of the spike RBD binding regions from the designed chimeric nanocages with the ACE2 receptor was highlighted. These data propose an effective multivalent synthetic nanocage, which might form the basis for new vaccine therapeutics designed against viruses such as SARS-CoV-2.

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Ferritin variants: inspirations for rationally designing protein nanocarriers

Abstract: Ferritin is endowed with a unique structure and the ability to self-assemble. Besides, genetic manipulation can easily tune the structure and functions of ferritin nanocages, which further expands the biomedical applications of ferritin.

Cited by 46 publications

References 81 publications

Bioengineered Dual‐Targeting Protein Nanocage for Stereoscopical Loading of Synergistic Hydrophilic/Hydrophobic Drugs to Enhance Anticancer Efficacy

Bioengineered Dual‐Targeting Protein Nanocage for Stereoscopical Loading of Synergistic Hydrophilic/Hydrophobic Drugs to Enhance Anticancer Efficacy

Exoskeleton for Biofunctionality Protection of Enzymes and Proteins for Intracellular Delivery

Multivalent Display of SARS-CoV-2 Spike (RBD Domain) of COVID-19 to Nanomaterial, Protein Ferritin Nanocages

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