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| Pàgina inicial > Articles > Articles publicats > Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering |
(Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat de Barcelona. Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals) (Institut d'Investigació Biomèdica Sant Pau) (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Institut d'Investigació Biomèdica Sant Pau)
| Data: | 2020 |
| Resum: | Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes self-assembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4 cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 interaction. All these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4 human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker. |
| Ajuts: | Ministerio de Ciencia e Innovación BIO2016-76063-R Instituto de Salud Carlos III PI15/00272 Instituto de Salud Carlos III PIE15//00028 Instituto de Salud Carlos III PI18/00650 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-865 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018/FI_B2_05051 Agència de Gestió d'Ajuts Universitaris i de Recerca 2019/FI_B_35252 |
| Nota: | Altres ajuts: EU COST Action CA 17140. Villaverde A received an ICREA ACADEMIA award. Unzueta was supported by PERIS program from the Health Department of la Generalitat de Catalunya. |
| Drets: | Tots els drets reservats.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió acceptada per publicar |
| Matèria: | Nanoparticles ; Protein materials ; Recombinant proteins ; Drug delivery ; Self-assembling ; Cancer cell targeting |
| Publicat a: | Science China Materials, Vol. 63, issue 1 (Jan. 2020), p. 147-156, ISSN 2199-4501 |
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