TY - JOUR
T1 - Gold Nanoparticle Size and Shape Effects on Cellular Uptake and Intracellular Distribution of siRNA Nanoconstructs
AU - Yue, Jun
AU - Feliciano, Timothy Joel
AU - Li, Wenlong
AU - Lee, Andrew
AU - Odom, Teri W.
N1 - Funding Information:
This work was supported by the Cancer Center of Nanotechnology Excellence (CCNE) of the NIH National Cancer Institute at Northwestern University (U54 CA199091, J.Y., A.L., T.W.O.). Fluorescence 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 were conducted at the Northwestern University Quantitative Bioelemental Imaging Center. We thank Charlene Wilke for processing samples for TEM. T.J.F. was supported in part by the Chemistry of Life Processes Predoctoral Training Program (5T32 GM105538-04); W.L. and T.J.F. were supported by the NTU-NU Institute for NanoMedicine located at the International Institute for Nanotechnology Northwestern University, U.S.A. and the Nanyang Technological University Singapore (Agmt 10/20/2014).
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/6/21
Y1 - 2017/6/21
N2 - 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, 50 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 50 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.
AB - 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, 50 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 50 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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U2 - 10.1021/acs.bioconjchem.7b00252
DO - 10.1021/acs.bioconjchem.7b00252
M3 - Article
C2 - 28574255
AN - SCOPUS:85021089462
VL - 28
SP - 1791
EP - 1800
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 6
ER -