Versatile platform for nanoparticle surface bioengineering based on SiO2-binding peptide and proteinaceous Barnase∗Barstar interface

Victoria O. Shipunova, Ivan V. Zelepukin, Oleg A. Stremovskiy, Maxim P. Nikitin, Andrew Care, Anwar Sunna, Andrei V. Zvyagin, Sergey M. Deyev

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Nanoparticle surface engineering can change its chemical identity to enable surface coupling with functional biomolecules. However, common surface coupling methods such as physical adsorption or chemical conjugation often suffer from the low coupling yield, poorly controllable orientation of biomolecules, and steric hindrance during target binding. These issues limit the application scope of nanostructures for theranostics and personalized medicine. To address these shortfalls, we developed a rapid and versatile method of nanoparticle biomodification. The method is based on a SiO 2 -binding peptide that binds to the nanoparticle surface and a protein adaptor system, Barnase∗Barstar protein pair, serving as a "molecular glue" between the peptide and the attached biomolecule. The biomodification procedure shortens to several minutes, preserves the orientation and functions of biomolecules, and enables control over the number and ratio of attached molecules. The capabilities of the proposed biomodification platform were demonstrated by coupling different types of nanoparticles with DARPin9.29 and 4D5scFv - molecules that recognize the human epidermal growth factor receptor 2 (HER2/neu) oncomarker - and by subsequent highly selective immunotargeting of the modified nanoparticles to different HER2/neu-overexpressing cancer cells in one-step or two-step (by pretargeting with HER2/neu-recognizing molecule) modes. The method preserved the biological activity of the DARPin9.29 molecules attached to a nanoparticle, whereas the state-of-the-art carbodiimide 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysulfosuccinimide method of conjugation led to a complete loss of the functional activity of the DARPin9.29 nanoparticle-protein complex. Moreover, the method allowed surface design of nanoparticles that selectively interacted with antigens in complex biological fluids, such as whole blood. The demonstrated capabilities show this method to be a promising alternative to commonly used chemical conjugation techniques in nanobiotechnology, theranostics, and clinical applications.

LanguageEnglish
Pages17437-17447
Number of pages11
JournalACS Applied Materials and Interfaces
Volume10
Issue number20
DOIs
Publication statusPublished - 23 May 2018

Fingerprint

Peptides
Nanoparticles
Biomolecules
Molecules
Proteins
Ethyldimethylaminopropyl Carbodiimide
Nanobiotechnology
Bacillus amyloliquefaciens ribonuclease
Bacillus amyloliquefaciens barstar protein
Bioengineering
Glues
Antigens
Bioactivity
Medicine
Nanostructures
Blood
Cells
Adsorption
Fluids

Keywords

  • nanoparticle modification
  • bioengineering
  • cancer cells
  • Barnase
  • Barstar
  • HER2/neu
  • targeted delivery
  • DARPin

Cite this

Shipunova, Victoria O. ; Zelepukin, Ivan V. ; Stremovskiy, Oleg A. ; Nikitin, Maxim P. ; Care, Andrew ; Sunna, Anwar ; Zvyagin, Andrei V. ; Deyev, Sergey M. / Versatile platform for nanoparticle surface bioengineering based on SiO2-binding peptide and proteinaceous Barnase∗Barstar interface. In: ACS Applied Materials and Interfaces. 2018 ; Vol. 10, No. 20. pp. 17437-17447.
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Versatile platform for nanoparticle surface bioengineering based on SiO2-binding peptide and proteinaceous Barnase∗Barstar interface. / Shipunova, Victoria O.; Zelepukin, Ivan V.; Stremovskiy, Oleg A.; Nikitin, Maxim P.; Care, Andrew; Sunna, Anwar; Zvyagin, Andrei V.; Deyev, Sergey M.

In: ACS Applied Materials and Interfaces, Vol. 10, No. 20, 23.05.2018, p. 17437-17447.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Versatile platform for nanoparticle surface bioengineering based on SiO2-binding peptide and proteinaceous Barnase∗Barstar interface

AU - Shipunova, Victoria O.

AU - Zelepukin, Ivan V.

AU - Stremovskiy, Oleg A.

AU - Nikitin, Maxim P.

AU - Care, Andrew

AU - Sunna, Anwar

AU - Zvyagin, Andrei V.

AU - Deyev, Sergey M.

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AB - Nanoparticle surface engineering can change its chemical identity to enable surface coupling with functional biomolecules. However, common surface coupling methods such as physical adsorption or chemical conjugation often suffer from the low coupling yield, poorly controllable orientation of biomolecules, and steric hindrance during target binding. These issues limit the application scope of nanostructures for theranostics and personalized medicine. To address these shortfalls, we developed a rapid and versatile method of nanoparticle biomodification. The method is based on a SiO 2 -binding peptide that binds to the nanoparticle surface and a protein adaptor system, Barnase∗Barstar protein pair, serving as a "molecular glue" between the peptide and the attached biomolecule. The biomodification procedure shortens to several minutes, preserves the orientation and functions of biomolecules, and enables control over the number and ratio of attached molecules. The capabilities of the proposed biomodification platform were demonstrated by coupling different types of nanoparticles with DARPin9.29 and 4D5scFv - molecules that recognize the human epidermal growth factor receptor 2 (HER2/neu) oncomarker - and by subsequent highly selective immunotargeting of the modified nanoparticles to different HER2/neu-overexpressing cancer cells in one-step or two-step (by pretargeting with HER2/neu-recognizing molecule) modes. The method preserved the biological activity of the DARPin9.29 molecules attached to a nanoparticle, whereas the state-of-the-art carbodiimide 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysulfosuccinimide method of conjugation led to a complete loss of the functional activity of the DARPin9.29 nanoparticle-protein complex. Moreover, the method allowed surface design of nanoparticles that selectively interacted with antigens in complex biological fluids, such as whole blood. The demonstrated capabilities show this method to be a promising alternative to commonly used chemical conjugation techniques in nanobiotechnology, theranostics, and clinical applications.

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