Virus-like nanoparticles as enzyme carriers for Enzyme Replacement Therapy (ERT)

González-Davis, Oscar; Villagrana-Escareño, María V.; Trujillo, Mario A.; Gama, Pedro; Chauhan, Kanchan; Vázquez-Duhalt, Rafael

doi:10.1016/j.virol.2023.01.017

Cited by 8 publications

(9 citation statements)

References 167 publications

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“…An emerging strategy to increase the enzyme half-life, preventing its degradation upon systemic administration, is the use of nanoparticles as enzyme carriers, which can be properly functionalized to release their bioactive cargo to the specific site of action. [65] In this perspective, GCase has been successfully encapsulated inside non-infectious virus-like nanoparticles (VLP's) functionalized with mannose groups to be specifically targeted to macrophage cells. [66] The encapsulated GCase was efficiently internalized in the cells, resulting in a significant increase of its activity.…”

Section: Enzyme Replacement Therapymentioning

confidence: 99%

Gaucher Disease: A Glance from a Medicinal Chemistry Perspective

Prencipe,

Barzan,

Savian

et al. 2024

ChemMedChem

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Rare diseases are particular pathological conditions affecting a limited number of people and few drugs are known to be effective as therapeutic treatment. Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, belongs to this class of disorders, and it is considered the most common among the Lysosomal Storage Diseases. The two main therapeutic approaches are the Enzyme Replacement Therapy (ERT) and the Substrate Reduction Therapy (SRT). ERT, consisting in replacing the defective enzyme by administering a recombinant enzyme, is effective in alleviating the visceral symptoms, hallmarks of the most common subtype of the disease whereas it has no effects when symptoms involve CNS, since the recombinant protein is unable to significantly cross the Blood Brain Barrier. The SRT strategy involves inhibiting glucosylceramide synthase (GCS), the enzyme responsible for the production of the associated storage molecule. The rational design of new inhibitors of GCS has been hampered by the lack of either the crystal structure of the enzyme or an in‐silico model of the active site which could provide important information regarding the interactions of potential inhibitors with the target, but, despite this, interesting results have been obtained and are herein reviewed.

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Section: Enzyme Replacement Therapymentioning

confidence: 99%

Gaucher Disease: A Glance from a Medicinal Chemistry Perspective

Prencipe,

Barzan,

Savian

et al. 2024

ChemMedChem

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“…155 More excitingly, they have shown tremendous promise for biomedical applications, owing to their versatility, high stability, and biosafety. To this end, both genetic and chemical methods have been employed for targeting specific cells, prolonging blood circulatory half-life, 156,157 avoiding protease degradation, and escaping immune detection. VLPs-based nanoreactors have been utilized to integrate with living cells to restore lost functions or to introduce new functions into living cells for enzyme replacement therapy (ERT); 157 they have also shown profound potential for targeted cancer cells chemotherapy via enzyme prodrug activation (EPT).…”

Section: Potential Applications Of Vlpsbased Nanoreactors In Biomedicinementioning

confidence: 99%

“…To this end, both genetic and chemical methods have been employed for targeting specific cells, prolonging blood circulatory half-life, 156,157 avoiding protease degradation, and escaping immune detection. VLPs-based nanoreactors have been utilized to integrate with living cells to restore lost functions or to introduce new functions into living cells for enzyme replacement therapy (ERT); 157 they have also shown profound potential for targeted cancer cells chemotherapy via enzyme prodrug activation (EPT). 63 A variety of studies have demonstrated that VLPs-based nanoreactors can successfully replicate the role of metabolic enzymes for ERT.…”

Section: Potential Applications Of Vlpsbased Nanoreactors In Biomedicinementioning

confidence: 99%

Virus-like particles nanoreactors: from catalysis towards bio-applications

Su,

Liu,

Huang

et al. 2023

J. Mater. Chem. B

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“…[20,21] VLPs are widely used in vaccine technology and have recently been proposed as nanocarriers of drugs for different biomedical therapies. [22][23][24][25] VLPs can be derived from native viruses or obtained by recombinant technology. After removing the genetic material, the purified monomeric coat protein (CP) is self-assembled under certain conditions forming hollow nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

“…VLPs can contain active enzymes, and the arrangement is called an enzymatic nanoreactor. [22] Improved catalytic properties have been reported for virus-based enzymatic nanoreactors. [30][31][32] VLP-based enzymatic nanoreactors containing cytochrome P450 activity have been proposed for prodrug activation in breast cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Glucose oxidase virus‐based nanoreactors for smart breast cancer therapy

Gama

Juàrez

Rodríguez-Hernández

et al. 2023

Biotechnology Journal

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BackgroundBreast cancer is the most common malignant tumor disease and the leading cause of female mortality. The evolution of nanomaterials science opens the opportunity to improve traditional cancer therapies, enhancing therapy efficiency and reducing side effects.Methods and major resultsHerein, protein cages conceived as enzymatic nanoreactors were designed and produced by using virus‐like nanoparticles (VLPs) from Brome mosaic virus (BMV) and containing the catalytic activity of glucose oxidase (GOx) enzyme. The GOx enzyme was encapsulated into the BMV capsid (VLP‐GOx), and the resulting enzymatic nanoreactors were coated with human serum albumin (VLP‐GOx@HSA) for breast tumor cell targeting. The effect of the synthesized GOx nanoreactors on breast tumor cell lines was studied in vitro. Both nanoreactor preparations VLP‐GOx and VLP‐GOx@HSA showed to be highly cytotoxic for breast tumor cell cultures. Cytotoxicity for human embryonic kidney cells was also found. The monitoring of nanoreactor treatment on triple‐negative breast cancer cells showed an evident production of oxygen by the catalase antioxidant enzyme induced by the high production of hydrogen peroxide from GOx activity.Conclusions and implicationsThe nanoreactors containing GOx activity are entirely suitable for cytotoxicity generation in tumor cells. The HSA functionalization of the VLP‐GOx nanoreactors, a strategy designed for selective cancer targeting, showed no improvement in the cytotoxic effect. The GOx containing enzymatic nanoreactors seems to be an interesting alternative to improve the current cancer therapy. In vivo studies are ongoing to reinforce the effectiveness of this treatment strategy.

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Virus-like nanoparticles as enzyme carriers for Enzyme Replacement Therapy (ERT)

Cited by 8 publications

References 167 publications

Gaucher Disease: A Glance from a Medicinal Chemistry Perspective

Gaucher Disease: A Glance from a Medicinal Chemistry Perspective

Virus-like particles nanoreactors: from catalysis towards bio-applications

Glucose oxidase virus‐based nanoreactors for smart breast cancer therapy

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