Tumor-Homing, Size-Tunable Clustered Nanoparticles for Anticancer Therapeutics
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- Tumor-Homing, Size-Tunable Clustered Nanoparticles for Anticancer Therapeutics
- Jinhwan Kim; Yeong Mi Lee; Youngnam Kang; Won Jong Kim
- ACS NANO, v.8, no.9, pp.9358 - 9367
- AMER CHEMICAL SOC
- We present herein a pH-responsive dynamic DNA nanocluster based on gold nanoparticles with highly packed nucleic acid 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 nanoparticles with bcl-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 cluster into single gold nanoparticles in response to the pH decrease in the late endosome. Furthermore, the antiapoptotic Bcl-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 acid-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.
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