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Deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model

Because of their high specificity and low side effects, protein drugs possess a substantial global market. However, the low bioavailability of protein is still a major obstacle to their expanded applications, which is expected to be answered with proper protein formulations. Taking corneal neovascul...

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Autores principales: Xu, H., Tang, B., Huang, W., Luo, S., Zhang, T., Yuan, J., Zheng, Q., Zan, X.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569714/
https://www.ncbi.nlm.nih.gov/pubmed/34765961
http://dx.doi.org/10.1016/j.mtbio.2021.100143
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author Xu, H.
Tang, B.
Huang, W.
Luo, S.
Zhang, T.
Yuan, J.
Zheng, Q.
Zan, X.
author_facet Xu, H.
Tang, B.
Huang, W.
Luo, S.
Zhang, T.
Yuan, J.
Zheng, Q.
Zan, X.
author_sort Xu, H.
collection PubMed
description Because of their high specificity and low side effects, protein drugs possess a substantial global market. However, the low bioavailability of protein is still a major obstacle to their expanded applications, which is expected to be answered with proper protein formulations. Taking corneal neovascularization (CNV) as an example, we demonstrated a co-assembled system of hexa-histidine and Ava (Avastin) with metal ions (HmA@Ava) could cross the cornea, the most important bio-barrier during the treatment of most diseases of the anterior segment in clinics. We found that the nanosized HmA@Ava efficiently encapsulated Ava with impressive loading capacity without destroying the bioactivity of Ava and assisted Ava penetration through the corneal barriers to effectively inhibit CNV development in an alkali burn rat model with sustained and pH-dependent Ava release. Our results suggested that the co-assembled strategy of protein and HmA is a proper formulation to protein drugs, with promising penetration ability to deliver protein across bio-barriers, which could open a path for topical administration of protein drugs for treatment of various ocular diseases and hold enormous potential for delivery of therapeutic proteins not only for ocular diseases but also for other diseases that require protein treatment.
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spelling pubmed-85697142021-11-10 Deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model Xu, H. Tang, B. Huang, W. Luo, S. Zhang, T. Yuan, J. Zheng, Q. Zan, X. Mater Today Bio Full Length Article Because of their high specificity and low side effects, protein drugs possess a substantial global market. However, the low bioavailability of protein is still a major obstacle to their expanded applications, which is expected to be answered with proper protein formulations. Taking corneal neovascularization (CNV) as an example, we demonstrated a co-assembled system of hexa-histidine and Ava (Avastin) with metal ions (HmA@Ava) could cross the cornea, the most important bio-barrier during the treatment of most diseases of the anterior segment in clinics. We found that the nanosized HmA@Ava efficiently encapsulated Ava with impressive loading capacity without destroying the bioactivity of Ava and assisted Ava penetration through the corneal barriers to effectively inhibit CNV development in an alkali burn rat model with sustained and pH-dependent Ava release. Our results suggested that the co-assembled strategy of protein and HmA is a proper formulation to protein drugs, with promising penetration ability to deliver protein across bio-barriers, which could open a path for topical administration of protein drugs for treatment of various ocular diseases and hold enormous potential for delivery of therapeutic proteins not only for ocular diseases but also for other diseases that require protein treatment. Elsevier 2021-10-01 /pmc/articles/PMC8569714/ /pubmed/34765961 http://dx.doi.org/10.1016/j.mtbio.2021.100143 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Xu, H.
Tang, B.
Huang, W.
Luo, S.
Zhang, T.
Yuan, J.
Zheng, Q.
Zan, X.
Deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model
title Deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model
title_full Deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model
title_fullStr Deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model
title_full_unstemmed Deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model
title_short Deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model
title_sort deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569714/
https://www.ncbi.nlm.nih.gov/pubmed/34765961
http://dx.doi.org/10.1016/j.mtbio.2021.100143
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