Nano Research

, Volume 12, Issue 4, pp 889–896 | Cite as

Regulation of the cellular uptake of nanoparticles by the orientation of helical polypeptides

  • Chong Zhang
  • Jianhua Lu
  • Falin Tian
  • Lindong Li
  • Yingqin Hou
  • Yaoyi Wang
  • Lingdong SunEmail author
  • Xinghua ShiEmail author
  • Hua LuEmail author
Research Article


Controlling the cellular interaction and internalization of polymer-modified nanoparticles (NPs) is of central importance to the development of promising nanomedicines. Here, we describe the use of synthetic polypeptides for NP surface coating and regulation of their cellular uptake behaviors by simply switching the conformation and anchoring orientation. Our results show that gold NPs (AuNPs) coated with a helical poly(γ-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)esteryl L-glutamate) (L-P(EG3Glu)50) from the C-terminus ((L-C)-AuNPs) exhibit greater zeta potential and more cellular uptake (2.0–5.5 fold higher) than those coated with the same polypeptide but anchored from the N-terminus ((L-N)-AuNPs), or from both the C- and N-terminus at a 1/1 molar ratio ((L-C/L-N)-AuNPs). A similar orientation-regulated cellular internalization pattern is observed in D-P(EG3Glu)50 but not the unstructured DL-P(EG3Glu)50-modified AuNPs, suggesting an important and universal role of the helix-derived macrodipole in cellular uptake. Moreover, this orientation-governed internalization is successfully reproduced in P(EG3Glu)50-coated gold nanorods (AuNRs), and applied to the design of doxorubicin-loaded polypeptide micelles. Simulation study offers time-resolved insights regarding the NP–membrane interactions and membrane remodeling. Thus, our study provides a delicate way of regulating the surface chemistry of NPs and the subsequent NP–cell interactions. Moreover, the results highlight the uniqueness of polypeptides in NP surface engineering, and urge a more careful consideration on the polymer orientation effect.


helix orientation polypeptides cellular uptake gold nanoparticles 


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Financial supports from the National Key Research and Development Program of China (No. 2016YFA0201400) and the National Natural Science Foundation of China (No. 21722401) are gratefully acknowledged.

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Regulation of the cellular uptake of nanoparticles by the orientation of helical polypeptides


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Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular EngineeringPeking UniversityBeijingChina
  2. 2.Center for Soft Matter Science and Engineering, Key Laboratory of Polymer Chemistry and Physics of Ministry of EducationPeking UniversityBeijingChina
  3. 3.CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina
  4. 4.State Key Laboratory of Rare Earth Materials Chemistry and Applications, PKU-HKU Joint Laboratory in Rare Earth Materials and Bioinorganic ChemistryPeking UniversityBeijingChina

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