Journal
BIOCONJUGATE CHEMISTRY
Volume 28, Issue 6, Pages 1791-1800Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.7b00252
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Funding
- Cancer Center of Nano technology Excellence (CCNE) of the NIH National Cancer Institute at Northwestern University [U54 CA199091]
- Chemistry of Life Processes Predoctoral Training Program [5 T32 GM105538-04]
- NTU-NU Institute for NanoMedicine located at the International Institute for Nanotechnology, Northwestern University, U.S.A.
- Nanyang Technological University, Singapore
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Gold nanoparticles (AuNPs) show potential for transfecting target cells with small interfering RNA (siRNA), but the influence of key design parameters such as the size and shape of the particle core is incomplete. This paper describes a side-by-side comparison of the in vitro response of U87 glioblastoma cells to different formulations of siRNA-conjugated gold nanoconstructs targeting the expression of isocitrate dehydrogenase 1 (IDH1) based on 13 nm spheres, 50 nm spheres, and 40 nm stars. 50 nm spheres and 40 nm stars showed much higher uptake efficiency compared to 13 nm spheres. Confocal fluorescence microscopy showed that all three formulations were localized in the endosomes at early incubation times (2 h), but after 24 h, SO nm spheres and 40 nm stars were neither in endosomes nor in lysosomes while 13 nm spheres remained in endosomes. Transmission electron microscopy images revealed that the 13 nm spheres were enclosed and dispersed within endocytic vesicles while SO nm spheres and 40 nm stars were aggregated, and some of these NPs were outside of endocytic vesicles. In our comparison of nanoconstructs with different sizes and shapes, while holding siRNA surface density and nanoparticle concentration constant, we found that larger particles (50 nm spheres and 40 nm stars) showed higher potential as carriers for the delivery of siRNA.
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