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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4550-4555 |
| Number of pages | 6 |
| Journal | Journal of the American Chemical Society |
| Volume | 143 |
| Issue number | 12 |
| DOIs | |
| State | Published - Mar 31 2021 |
Funding
This work was supported by the National Institute of Health (NIH) under awards 5 R01 GM131421-02 (P.C., T.L., T.W.O.) and 1R01GM115763. This work made use of the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern’s MRSEC program (NSF DMR-1720139). Proteomics services were performed by the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center, instrumentation award (S10OD025194) from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569. Metal analysis was performed at the Northwestern University Quantitative Bio-element Imaging Center generously supported by NASA Ames Research Center NNA06CB93G. We are grateful for the support from Northwestern University High Throughput Analysis Laboratory.
ASJC Scopus subject areas
- General Chemistry
- Biochemistry
- Catalysis
- Colloid and Surface Chemistry
