Membrane-curvature-mediated co-endocytosis of bystander and functional nanoparticles

Kejie He, Yushuang Wei, Zhihong Zhang, Haibo Chen, Bing Yuan, Hong Bo Pang, Kai Yang

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Efficient cellular uptake of nanoparticles (NPs) is necessary for the development of nanomedicine in biomedical applications. Recently, the coadministration of functionalized NPs (FNPs) was shown to stimulate the cellular uptake of nonfunctionalized NPs (termed bystander NPs, BNPs), which presents a new strategy to achieve synergistic delivery. However, a mechanistic understanding of the underlying mechanism is still lacking. In this work, the bystander uptake effect was investigated at the cell membrane level by combining the coarse-grained molecular dynamics, potential of mean force calculation and theoretical energy analysis methods. The membrane internalization efficiency of BNPs was enhanced by co-administered FNPs, and such activity depends on the affinity of both NPs to the membrane and the resultant membrane deformation. The membrane-curvature-mediated attraction and aggregation of NPs facilitated the membrane uptake of BNPs. Furthermore, quantitative suggestions were given to modulate the BNP internalization through controlling the FNP properties such as size, concentration and surface-ligand density. Our results provide insight into the molecular mechanism of the bystander uptake effect, and offer a practical guide to regulate the cellular internalization of NPs for targeted and efficient delivery to cells.

Original languageEnglish (US)
Pages (from-to)9626-9633
Number of pages8
Issue number21
StatePublished - Jun 7 2021

Bibliographical note

Funding Information:
This work was financially supported by the National Natural Science Foundation of China (No. 21774092, U1532108, and U1932121), the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, National Institute of Health of USA (R01CA214550, R01GM133885), and the State of Minnesota (MNP#19.08).

Publisher Copyright:
© The Royal Society of Chemistry.


  • Cell Membrane
  • Endocytosis
  • Ligands
  • Molecular Dynamics Simulation
  • Nanoparticles

PubMed: MeSH publication types

  • Journal Article


Dive into the research topics of 'Membrane-curvature-mediated co-endocytosis of bystander and functional nanoparticles'. Together they form a unique fingerprint.

Cite this