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

• Published in: Nano research 2019-04, Vol.12 (4), p.889-896
• Main Authors: Zhang, Chong, Lu, Jianhua, Tian, Falin, Li, Lindong, Hou, Yingqin, Wang, Yaoyi, Sun, Lingdong, Shi, Xinghua, Lu, Hua
• Format: Article
• Language: English
• Subjects: Anchoring; Atomic/Molecular Structure and Spectra; Biomedicine; Biotechnology; C-Terminus; Cell interactions; Chemistry and Materials Science; Coating; Coatings; Condensed Matter Physics; Conformation; Doxorubicin; Glutamic acid; Gold; Internalization; Materials Science; Membranes; Micelles; N-Terminus; Nanoparticles; Nanorods; Nanotechnology; Organic chemistry; Orientation effects; Polymers; Polypeptides; Research Article; Surface chemistry; Zeta potential
• ISSN: 1998-0124; 1998-0000
• DOI: 10.1007/s12274-019-2319-6

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(EG 3 Glu) 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(EG 3 Glu) 50 but not the unstructured DL -P(EG 3 Glu) 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(EG 3 Glu) 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.