Engineering protein venoms as self-assembling CXCR4-targeted cytotoxic nanoparticles
Serna, Naroa (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Cano-Garrido, Olivia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Sánchez-García, Laura (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Pesarrodona Roches, Mireia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Unzueta Elorza, Ugutz (Institut d'Investigació Biomèdica Sant Pau)
Sánchez Chardi, Alejandro (Universitat Autònoma de Barcelona. Servei de Microscòpia)
Mangues, Ramon 1957- (Institut d'Investigació Biomèdica Sant Pau)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia

Date:	2020
Abstract:	Protein venoms are effective cytotoxic molecules that when conveniently targeted to tumoral markers can be exploited as promising anticancer drugs. Here, it is explored whether the structurally unrelated melittin, gomesin, and CLIP71 could be functionally active when engineered, in form of GFP fusions, as self-assembling multimeric nanoparticles. Incorporated in modular constructs including a C-terminal polyhistidine tag and an N-terminal peptidic ligand of the cytokine receptor CXCR4 (overexpressed in more than 20 human neoplasias), these venoms are well produced in recombinant bacteria as proteolytically stable regular nanoparticles ranging between 12 and 35 nm. Being highly fluorescent, these materials selectively penetrate, label, and kill CXCR4 tumor cells in a CXCR4-dependent fashion. The obtained data support the concept of recombinant venoms as promising drugs, through the precise formulation as tumor-targeted nanomaterials for selective theragnostic applications in CXCR4 cancers.
Grants:	Ministerio de Ciencia e Innovación BIO2016-76063-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-865 Instituto de Salud Carlos III PI15/00272 Instituto de Salud Carlos III PIE15/00028 Instituto de Salud Carlos III PI18/00650 Instituto de Salud Carlos III CP19/00028
Note:	Altres ajuts: to EU COST Action CA 17140 and ICREA ACADEMIA.
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Published in:	Particle & particle systems characterization, Vol. 37, Issue 6 (June 2020) , art. 2000040, ISSN 1521-4117

DOI: 10.1002/ppsc.202000040

Postprint 19 p, 701.6 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
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Articles > Published articles