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This paper describes how in vitro efficacy of aptamer-loaded gold nanostars (Apt-AuNS) can be enhanced by the increased loading of a G-quadruplex homodimer AS1411 (Apt) on the AuNS surface. In a low pH buffer environment, the loading density of Apt on AuNS was increased up to 2.5 times that obtained using the conventional salt-aging process. These highly loaded AuNS nanoconstructs (*Apt-AuNS) were taken up in pancreatic cancer and fibrosarcoma cells ca. 2 times more and at faster rates compared to Apt-AuNS. When a similar number of AuNS carriers was internalized by the cancer cells, the amount of AS1411 delivered via *Apt-AuNS was effectively double that of Apt-AuNS, and *Apt-AuNS resulted in an average of 42% increase in cell death. These results suggest that increasing the loading density on AuNS could provide a simple means to improve uptake as well as in vitro efficacy of the nanoconstructs in cancer cells.

Improved in Vitro Efficacy of Gold Nanoconstructs by Increased Loading of G-quadruplex Aptamer