Engineering a recombinant chlorotoxin as cell-targeted cytotoxic nanoparticles
Díaz, Raquel (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")
Serna, Naroa (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Sánchez Chardi, Alejandro (Universitat Autònoma de Barcelona. Servei de Microscòpia)
Cano-Garrido, Olivia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Sanchez, Julieta M. (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Unzueta Elorza, Ugutz (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. Departament de Genètica i de Microbiologia)

Date:	2019
Abstract:	The controlled oligomerization of functional proteins at the nanoscale offers the possibility to design and produce, by recombinant DNA technologies and in cell factories, improved materials and drugs in form of nanoparticles. A recombinant version of the scorpion toxin chlorotoxin (CTX), which has attracted interest due to its ability to preferentially bind cancer cells, has been engineered to self-assemble as regular 12 nm-nanoparticles that penetrate cultured cells with the same receptor-specificity than the natural toxin. These materials, that appear as promising, biocompatible and biodegradable drug carriers for cell-targeted therapy of glioma also exhibit a mild but still significant cytotoxic activity associated to the recombinant toxin, that simultaneously acts as both driver and therapeutic agent. In addition, the manipulation of the CTX-flanking regions shows a potent impact on the performance of the nanoparticles, supporting a high functional versatility of CTX-based constructs, regulatable by conventional genetic engineering and adaptable to specific therapeutic situations.
Grants:	Agencia Estatal de Investigación BIO2016-76063-R Ministerio de Economía y Competitividad PI15/00272 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018/FI_B2_00051
Note:	Altres ajuts: CIBER-BBN (project VENOM4CANCER) granted to AV.NS was supported by a predoctoral fellowship from the Government of Navarra, and UU is supported by PERIS program from the health department of la Generalitat de Cataluña. AV received an ICREA ACADEMIA award.
Rights:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Recombinant proteins ; Nanoparticles ; Cancer therapies ; Targeted therapies
Published in:	Science China Materials, Vol. 62, issue 6 (June 2019) , p. 892-898, ISSN 2199-4501

DOI: 10.1007/s40843-018-9391-y

Article. Postprint 13 p, 260.3 KB

Figura 1 1 p, 232.5 KB

Figura 2 1 p, 109.7 KB

Figura 3 1 p, 160.4 KB

Informació suplementària 7 p, 100.4 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