Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 31;143(12):4550-4555.
doi: 10.1021/jacs.1c00850. Epub 2021 Mar 18.

Nanoparticle Shape Determines Dynamics of Targeting Nanoconstructs on Cell Membranes

Priscilla Choo, Tingting Liu, Teri W Odom

Nanoparticle Shape Determines Dynamics of Targeting Nanoconstructs on Cell Membranes

Priscilla Choo et al. J Am Chem Soc. .

Abstract

Nanoparticle carriers are effective drug delivery vehicles. Along with other design parameters including size, composition, and surface charge, particle shape strongly influences cellular uptake. How nanoparticle geometry affects targeted delivery under physiologically relevant conditions, however, is inconclusive. Here, we demonstrate that nanoconstruct core shape influences the dynamics of targeting ligand-receptor interactions on cancer cell membranes. By single-particle tracking of translational and rotational motion, we compared DNA aptamer AS1411 conjugated gold nanostars (AS1411-AuNS) and 50 nm gold spheres (AS1411-50NPs) on cells with and without targeted nucleolin membrane receptors. On nucleolin-expressing cells, AS1411-AuNS exhibited faster velocities under directed diffusion and translated over larger areas during restricted diffusion compared to AS1411-50NPs, despite their similar protein corona profiles. On nucleolin-inhibited cells, AS1411-AuNS showed faster rotation dynamics over smaller translational areas, while AS1411-50NPs did not display significant changes in translation. These differences in translational and rotational motions indicate that nanoparticle shape affects how targeting nanoconstructs bind to cell-membrane receptors.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.. Multi-channel live-cell imaging of AS1411-nanoconstructs on cell membrane.
SEM and DIC images of (a) AuNS and (b) 50NP taken at 0°, 45°, 90°, 135°, and 180°. DIC images: 2 μm × 2 μm, SEM images: 200 nm × 200 nm. (c) DIC light path of AS1411-AuNS and an example DIC image. (d) DIC-epifluorescence light path for tracking AS1411-50NPs and representative DIC and epifluorescence image. DM: dichroic mirror, RM: reflecting mirror.
Figure 2.
Figure 2.. Rotational Dynamics AS1411-AuNS on NCL+ and NCL− MCF-7 cells.
DIC images of AS1411-AuNS on (a) NCL+ and (b) NCL− cell membranes. (c, d) Plots of DIC contrast for the two particles in (a, b) over the whole 30-s stream. (e) Comparison of maximum duration for AS1411-AuNS. (NCL+: N = 56, NCL−: N = 38) Statistical significance: ***p < 0.001, student t-test.
Figure 3.
Figure 3.. Categorizing diffusion modes via MSD fitting.
(a) Representative MSD fitting. Raw data (dots) were fit with corresponding equations (solid lines). (b) Representative trajectories for AS1411-AuNS/NCL+, AS1411-AuNS/NCL−, AS1411-50NPs/NCL+, and AS1411-50NPs/NCL−.
Figure 4.
Figure 4.. Impact of NP shape on nanoconstruct translations.
(a-d) Translational mode distribution for AS1411-AuNS/NCL+, AS1411-AuNS/NCL−, AS1411-50NPs/NCL+ (N = 45), and AS1411-50NPs/NCL− (N = 34). (e) Velocity for AS1411-AuNS and AS1411-50NPs under DD on NCL+ MCF-7 cell membranes. (f) Confinement lengths for AS1411-AuNS and AS1411-50NPs under RD on NCL+ and NCL− MCF-7 cells. Statistical significance: **p < 0.01, ****p < 0.0001, one-way ANOVA.
Scheme 1.
Scheme 1.
Live-cell imaging of AS1411-AuNS and AS1411-50NPs on (left) NCL+ and (right) NCL− cancer cell membranes.
See this image and copyright information in PMC

References

    1. Xie X; Liao J; Shao X; Li Q; Lin Y, The Effect of shape on Cellular Uptake of Gold Nanoparticles in the forms of Stars, Rods, and Triangles. Sci Rep 2017, 7 (1), 3827. - PMC - PubMed
    1. Foroozandeh P; Aziz AA, Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles. Nanoscale Res Lett 2018, 13 (1), 339. - PMC - PubMed
    1. Lee K, Huang ZN, Mirkin CA, Odom TW, Endosomal Organization of CpG Constructs Correlates with Enhanced Immune Activation. Nano Letters 2020, 20 (8), 6170–6175. - PMC - PubMed
    1. Shah S, Liu Y, Hu W, Gao J, Modeling Particle Shape-Dependent Dynamics in Nanomedicine. J Nanosci Nanotechnol 2011, 11 (2), 919–928. - PMC - PubMed
    1. McKenzie M, Ha SM, Rammohan A, Radhakrishnan R, Ramakrishnan N, Multivalent Binding of a Ligand-Coated Particle: Role of Shape, Size, and Ligand Heterogeneity. Biophysical Journal 2018, 114 (8), 1830–1846. - PMC - PubMed

Publication types

LinkOut - more resources