A natural drug entry channel in the ferritin nanocage

Jiang, Bing; Chen, Xuehui; Sun, Guozhe; Chen, Xiangru; Yin, Yufang; Jin, Yiliang; Mei, Qian; Ma, L.; Yang, Yili; Yan, Xiyun; Fan, Kelong

doi:10.1016/j.nantod.2020.100948

Cited by 61 publications

(78 citation statements)

References 23 publications

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“…The hydrophilic EPI was first encapsulated into the inner cavity of the Am‐PNCage by thermal treatment through the hydrophilic drug entry channel induced. [ 32 ] The complex was then incubated with CPT, which bound to the hydrophobic P out peptide displayed on the outer surface of protein shell through hydrophobic interaction. The modification with the hydrophobic P out peptide overcomes the limitation of the hydrophilic nature of HFn, achieving the objective of effectively loading both hydrophilic and hydrophobic drugs on one protein nanocarrier.…”

Section: Resultsmentioning

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: Resultsmentioning

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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“…Conversion of Ft drug carriers in vivo is often impeded by the drug loading process's inefficiency and low yield [81]. Xiyun Yan [82] and his team found that natural drug entry channels in the shell of recombinant human H-Ft (HFn) are susceptible to temperature changes. Based on this, a simple drug delivery strategy counted on channels was developed to avoid the denaturation of HFn protein cage and denaturant.…”

Section: Nanoparticles Targeting Transferrin Receptorsmentioning

confidence: 99%

Research development in tumor therapy: role of iron-related nanoparticles

Dai

2021

E3S Web Conf.

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As an essential nutrient element for life, iron’s metabolic balance in body tissues is crucial to sustaining normal physiological functions, and it is inextricably related to tumors. Nanotechnology is gaining much attention around the world for cancer treatment. Considering the critical role of iron metabolism, nanocarriers’ toxicity and biocompatibility, novel nanomaterials based on the biochemical activity of iron and the regulatory proteins of iron homeostasis-metabolism show broad application prospects in the field of tumor diagnosis and treatment. In this review, the role of iron-related nanocarriers for tumor therapy, such as iron oxide nanoparticles, Fe-based metal-organic frameworks, ferritin, and transferrin, was reviewed, aiming to help people better understand their tremendous potential in tumor therapy.

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“…Accordingly, ferritins are among the most studied protein nanosystems. They typically display a quaternary structure characterized by a hollow spherical cage with an internal cavity large enough to host different cargoes including drugs, imaging agents, small proteins, and nucleic acids [12][13][14][15][16][17][18]. Special attention is currently focused on human H ferritin for its ability to recognize the CD71 receptor, typically overexpressed in cancer cells [19].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Background In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells. Results Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation. Conclusion The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells. Graphic abstract

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A natural drug entry channel in the ferritin nanocage

Cited by 61 publications

References 23 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

Research development in tumor therapy: role of iron-related nanoparticles

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

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