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Engineering a recombinant chlorotoxin as cell-targeted cytotoxic nanoparticles

  • Raquel Díaz
  • Laura Sánchez-García
  • Naroa Serna
  • Alejandro Sánchez-Chardi
  • Olivia Cano-Garrido
  • Julieta M. Sánchez
  • Ugutz UnzuetaEmail author
  • Esther Vazquez
  • Antonio VillaverdeEmail author
Letter
  • 38 Downloads

重组氯毒素构建细胞靶向的活性纳米颗粒

摘要

功能性蛋白质在纳米尺度的可控寡聚化提供了通过重组DNA技术来设计和生产改良材料和药物的可能性. 氯毒素(CTX), 作为一种 重组的蝎毒素, 由于其优先结合癌细胞的能力而引起人们的兴趣. 本研究将氯毒素设计并自组装为12 nm的常规纳米颗粒, 这些纳米颗粒 可穿透具有和天然毒素相同受体特异性的培养细胞. 这些生物相容且可生物降解的材料, 表现出与同时作为载体和治疗剂的重组毒素相 应的温和但仍然显著的细胞毒活性, 有希望成为用于细胞靶向治疗胶质瘤的药物载体. 此外, 对CTX侧区域的修改可有效影响纳米颗粒的 性能, 说明基于CTX的构建体可通过常规基因工程来调节其多重功能性.

Notes

Acknowledgements

This study has been funded by the Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (BIO2016-76063-R, AEI/FEDER, UE), AGAUR (2017SGR-229) and CIBER-BBN (project VENOM4CANCER) granted to Villaverde A, ISCIII (PI15/00272 co-founding FEDER) to Vázquez E. Protein production and DLS have been partially performed by the ICTS “NANBIOSIS”, more specifically by the Protein Production Platform of CIBER-BBN/IBB (https://doi.org/www.nanbiosis.es/unit/u1-protein-productionplatform-ppp/) and the Biomaterial Processing and Nanostructuring Unit (https://doi.org/www.nanbiosis.es/portfolio/u6-biomaterial-processing-andnanostructuring-unit/). Cytometry and cell culture experiments were performed at the Cytometry and Cell Culture Unit of the UAB (SCAC). Díaz R received an overseas predoctoral fellowship from Conacyt (Gobierno de México, 2016). Sánchez-Garcia L was supported by predoctoral fellowship from AGAUR (2018FI_B2_00051), Serna N was supported by a predoctoral fellowship from the Government of Navarra, and Unzueta U is supported by PERIS program from the health department of la Generalitat de Cataluña. Villaverde A received an ICREA ACADEMIA award.

Supplementary material

40843_2018_9391_MOESM1_ESM.pdf (124 kb)
Engineering a recombinant chlorotoxin as cell-targeted cytotoxic nanoparticles

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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Raquel Díaz
    • 1
    • 2
    • 3
  • Laura Sánchez-García
    • 1
    • 2
    • 3
  • Naroa Serna
    • 1
    • 2
    • 3
  • Alejandro Sánchez-Chardi
    • 4
  • Olivia Cano-Garrido
    • 1
    • 2
    • 3
  • Julieta M. Sánchez
    • 1
    • 2
    • 5
  • Ugutz Unzueta
    • 2
    • 6
    Email author
  • Esther Vazquez
    • 1
    • 2
    • 3
  • Antonio Villaverde
    • 1
    • 2
    • 3
    Email author
  1. 1.Institut de Biotecnologia i de BiomedicinaUniversitat Autònoma de BarcelonaBarcelonaSpain
  2. 2.Departament de Genètica i de MicrobiologiaUniversitat Autònoma de BarcelonaBarcelonaSpain
  3. 3.CIBER de BioingenieríaBiomateriales y Nanomedicina (CIBER-BBN)BarcelonaSpain
  4. 4.Servei de MicroscòpiaUniversitat Autònoma de BarcelonaBarcelonaSpain
  5. 5.Universidad Nacional de Córdoba, Facultad de Ciencias Exactas, Físicas y Naturales. ICTA and Departamento de Química, Cátedra de Química Biológica. Córdoba. Argentina. CONICETInstituto de Investigaciones Biológicas y Tecnológicas (IIBYT), Córdoba, Argentina.CórdobaArgentina
  6. 6.Biomedical Research Institute Sant Pau (IIB-Sant Pau) and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant PauBarcelonaSpain

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