Tumor-Homing, Size-Tunable Clustered Nanoparticles for Anticancer Therapeutics

We present herein a pH-responsive dynamic DNA nanoduster based on gold nanoparticles with highly packed nucleic add assembly and evaluate its potential as a drug delivery vehicle with tumor-specific accumulation. Each gold nanoparticle was readily functionalized with various functional DNA sequences; in particular, we modified the surface of gold nanopanicles with bd-2 antisense and i-motif binding sequences. Clustering of the gold nanoparticles induced by hybridization of each DNA sequence via i-motif DNA provided tumor targeting and drug loading capabilities. After cellular uptake, the drug was released by disassembly of the gold nanoparticle duster into single gold nanoparticles in response to the pH decrease in the late endosome. Furthermore, the andapoptotic Bd-2 protein was down-regulated by the antisense-modified gold nanoparticles; thus, drug-mediated apoptosis was significantly accelerated by sensitizing the cancer cells to the drug. Our size-tunable clustered nucleic add-grafted gold nanoparticles provide tumor homing in the blood circulation and are thus a potential multifunctional therapeutic agent in vivo as well as in vitro.