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  2. Uncovering the Importance of Ligand Mobility on Cellular Uptake of Nanoparticles: Insights from Experimental, Computational, and Theoretical Investigations

Uncovering the Importance of Ligand Mobility on Cellular Uptake of Nanoparticles: Insights from Experimental, Computational, and Theoretical Investigations

  • ACS Nano. 2024 Feb 12. doi: 10.1021/acsnano.3c11982.
Yuan-Qiang Chen 1 Meng-Die Xue 2 Jia-Li Li 2 Da Huo 2 Hong-Ming Ding 1 Yuqiang Ma 3
Affiliations

Affiliations

  • 1 Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou 215006, China.
  • 2 School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
  • 3 National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.
Abstract

The cellular uptake of nanoparticles (NPs) by biological cells is an important and fundamental process in Drug Delivery. Previous studies reveal that the physicochemical properties of nanoparticles as well as those of functionalized ligands can both critically affect the uptake behaviors. However, the effect of the conjugation strategy (i.e., the "bond" between the ligand and the NP) on the cellular uptake is overlooked and remains largely elusive. Here, by taking the broadly employed gold nanoparticle as an example, we comprehensively assessed the relationship between the conjugation strategy and uptake behaviors by introducing three ligands with the same functional terminal but different anchoring sites. As revealed by in vitro cell experiments and multiscale molecular simulations, the uptake efficiency of gold NPs was positively correlated with the strength of the "bond" and more specifically the ligand mobility on the NP surface. Moreover, we validated the results presented above by proposing a thermodynamic theory for the wrapping of NPs with mobile ligands. Further, we also showed that the endocytic pathway of NPs was highly dependent on ligand mobility. Overall, this study uncovered a vital role of conjugation strategy in the cellular uptake and may provide useful guidelines for tailoring the biobehaviors of nanoparticles.

Keywords

endocytosis; gold nanoparticle; ligand mobility; multiscale modeling; super-resolution imaging.

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