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. 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.

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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

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