Abstract
This paper reports how the endosomal pathways of nanoparticle (NP) constructs with different surface curvatures are affected by their order of delivery. Sequential incubation of cytosine-phosphate-guanine (CpG)-conjugated spiky and spherical gold NPs with macrophages resulted in different nanoconstruct ratios at the interior edges of endosomes. Application of spiky NPs after spherical NPs accelerated the formation of late-stage endosomes and resulted in larger endosomes, and the spherical NPs were enclosed by the spiky NPs. In contrast, the reverse incubation order produced an asymmetric distribution of the two nanoconstruct shapes in smaller endosomes. Macrophages with a higher proportion of the enclosed spherical NPs as well as a larger ratio of spiky to spherical NPs at the endosomal edge showed enhanced toll-like receptor 9 activation and secretion of proinflammatory cytokines and chemokines. Our results indicate that the subcellular trafficking of targeting nanoconstructs by vesicles is affected by both the delivery order and the endosomal distribution. Our study also establishes a new approach for nanoscale monitoring of intracellular therapeutics delivery with conventional electron microscopy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5274-5279 |
| Number of pages | 6 |
| Journal | Journal of the American Chemical Society |
| Volume | 144 |
| Issue number | 12 |
| DOIs | |
| State | Published - Mar 30 2022 |
Funding
This material is based on research sponsored by the National Institutes of Health (NIH) under Award 5 R01 GM131421-02 (K.L., T.W.O.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank Charlene Wilke for processing of TEM samples. Fluorescence and absorbance measurements were carried out in the High Throughput Analysis Laboratory. TEM imaging and confocal fluorescence imaging were performed at the Biological Imaging Facility. Gold analysis was conducted at the Northwestern University Quantitative Bioelemental Imaging Center generously supported by NASA Ames Research Center (NNA06CB93G). We appreciate the Mirkin group (Professor Chad Mirkin and Ziyin Huang) for letting us use their Luminex 200 instrument (InvitroGen, Carlsbad, CA) to measure cytokine levels. K.L. thanks Andrew Lee for helpful discussions.
ASJC Scopus subject areas
- General Chemistry
- Biochemistry
- Catalysis
- Colloid and Surface Chemistry