Endosomal escape of protein nanoparticles engineered through humanized histidine-rich peptides
Poly-histidine peptides such as H6 (HHHHHH) are used in protein biotechnologies as purification tags, pro- tein-assembling agents and endosomal-escape entities. The pleiotropic properties of such peptides make them appealing to design protein-based smart materials or nanoparticles for imaging or dru...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/179196 |
| Acceso en línea: | https://hdl.handle.net/2117/179196 https://dx.doi.org/10.1007/s40843-019-1231-y |
| Access Level: | acceso abierto |
| Palabra clave: | Biomathematics protein materials nanoparticles genetic design endosomal escape poly-histidines Biomatemàtica Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències |
| Sumario: | Poly-histidine peptides such as H6 (HHHHHH) are used in protein biotechnologies as purification tags, pro- tein-assembling agents and endosomal-escape entities. The pleiotropic properties of such peptides make them appealing to design protein-based smart materials or nanoparticles for imaging or drug delivery to be produced in form of re- combinant proteins. However, the clinical applicability of H6- tagged proteins is restricted by the potential immunogenicity of these segments. In this study, we have explored several humanized histidine-rich peptides in tumor-targeted modular proteins, which can specifically bind and be internalized by the target cells through the tumoral marker CXCR4. We were particularly interested in exploring how protein purification, self-assembling and endosomal escape perform in proteins containing the variant histidine-rich tags. Among the tested candidates, the peptide H5E (HEHEHEHEH) is promising as a good promoter of endosomal escape of the associated full- length protein upon endosomal internalization. The numer- ical modelling of cell penetration and endosomal escape of the tested proteins has revealed a negative relationship between the amount of protein internalized into target cells and the efficiency of cytoplasmic release. This fact demonstrates that the His-mediated, proton sponge-based endosomal escape saturates at moderate amounts of internalized protein, a fact that might be critical for the design of protein materials for cytosolic molecular delivery. |
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