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 that after 24 h, 50-nm spheres and 40-nm stars were neither in endosomes nor 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.

This paper describes how gold nanoparticle nanoconstructs can enhance anti-cancer effects of lysosomal targeting aptamers in breast cancer cells. Nanoconstructs consisting of anti-HER2 aptamer (human epidermal growth factor receptor 2, HApt) densely grafted on gold nanostars (AuNS) first targeted HER2 and then were internalized via HER2-mediated endocytosis. As incubation time increased, the nanoconstruct complexes were found in vesicular structures, starting from early endosomes to lysosomes as visualized by confocal fluorescence and differential interference contrast microscopy. Within the target organelle, lysosomes, HER2 was degraded by enzymes at low pH, which resulted in apoptosis. At specific time points related to the doubling time of the cancer cells, we found that accumulation of HER2-HApt-AuNS complexes in lysosomes, lysosomal activity, and lysosomal degradation of HER2 were positively correlated. Increased HER2 degradation by HApt-AuNS triggered cell death and cell cycle arrest in the G0/G1 phase inhibition of cell proliferation. This work shows how a perceived disadvantage of nanoparticle-based therapeutics—the inability of nanoconstructs to escape from vesicles and thus induce a biological response—can be overcome by both targeting lysosomes and exploiting lysosomal degradation of the biomarkers.

In this study, we develop a facile and efficient method for period-decorating carbon nanotubes (CNTs) using a supercritical (SC) CO 2 antisolvent-induced polymer epitaxy (SAIPE) method. It helps the epitaxy growth of PE on CNTs under a series of suitable experimental conditions, forming a nanohybrid shish-kebab (NHSK) structure. With the variation of a series of experimental conditions or peripheral effect, such as different solvent, PE concentration, CNTs concentration and SC CO 2 pressure, the NHSK structure, i.e., the size of the lamellae and the interval between them along the stem, can be varied. When p-xylene was used as the solvent for PE and single-walled CNT (SWCNT), the size of the lamellae can be adjusted from 80-120 to 125-250 nm with the change of the PE concentration. Using the same solvent p-xylene, with the change of SC CO 2 pressure, the size of the lamellae can be changed from 125-250 to 300-400 nm. When dichlorobenzene (DCB) was used as the solvent for PE and SWCNT, with the increase of the SWCNT concentration, from 0.002 to 0.006 and 0.01 wt %, the size of the lamellae can be reduced from 305-420 to 280-400 and 85-200 nm. In comparison to the experimental result with p-xylene used as the solvent, it is found that the decorated CNTs have more excellent dispersion when DCB was used as the solvent. Our experimental results indicate that the SAIPE method is effective for both SWCNTs and multiwalled CNTs (MWCNTs). Therefore, this work not only provides a new route to periodically functionalize CNTs with a controllable and adjustable method, but also it can be anticipated to open a gateway for making use of peculiar properties of SC CO 2 to help functionalize CNTs in an environmentally benign manner.

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