title: Tumor-homing, size-tunable clustered nanoparticles for anticancer therapeutics.
abstract: 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.
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science (IBS) , Pohang 790-784, Korea.
authors.forename: Jinhwan
authors.initials: J
authors.lastname: Kim
authors.forename: Yeong Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Youngnam
authors.initials: Y
authors.lastname: Kang
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D016373:DNA, Antisense / Q000737:chemistry / Q000235:genetics; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D006046:Gold / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D059372:Nucleotide Motifs; D010316:Particle Size
chemical_list: D000970:Antineoplastic Agents; D016373:DNA, Antisense; D004337:Drug Carriers; D006046:Gold; D004317:Doxorubicin
keywords: DNA nanotechnology; antisense; drug delivery; gold nanoparticle; i-motif