title: The effective nuclear delivery of doxorubicin from dextran-coated gold nanoparticles larger than nuclear pores.
abstract: To date, gold nanoparticles (AuNPs) have been investigated for diverse bioapplications. Generally, AuNPs are engineered to possess surface coating with organic/inorganic shells to increase colloidal stability in biological solutions and to facilitate chemical conjugation. In the present study, we developed a strategy to prepare dextran-coated AuNPs with control over its size by simply boiling an aqueous solution of Au salt and dextran, in which dextran serves as both reducing agent for AuNP (Au(0)) formation from Au(III) and AuNP surface coating material. The prepared dextran-coated AuNPs (dAuNPs) maintained its colloidal stability under high temperature, high salt concentration, and extreme pH. Importantly, the dAuNP remarkably improved efficacy of an anti-cancer agent, doxorubicin (Dox), when harnessed as a Dox delivery carrier. The half-maximal inhibitory concentration (EC50) of Dox-conjugated dAuNP with diameter of 170 nm was ∼9 pM in HeLa cells, which was 1.1 × 10(5) times lower than that of free Dox and lower than any previously reported values of Dox-nanoparticle complex. Interestingly, smaller AuNPs with 30 and 70 nm showed about 10 times higher EC50 than 170 nm AuNPs when treated to HeLa cells after conjugation with Dox. To achieve high cytotoxicity as cancer therapeutics, Dox should be delivered into nucleus to intercalate with DNA double helix. We show here that Dox-AuNPs was far more efficient as an anti-cancer drug than free Dox by releasing from AuNPs through spontaneous degradation of dextran, allowing free diffusion and nuclear uptake of Dox. We also revealed that larger AuNPs with lower degree of dextran crosslinking promoted faster degradation of dextran shells.
authors: Department of Chemistry and KI for the NanoCentury, KAIST, Daejeon 305-701, Republic of Korea.
authors: Hongje
authors: H
authors: Jang
authors: Soo-Ryoon
authors: SR
authors: Ryoo
authors: Kostas
authors: K
authors: Kostarelos
authors: Sang Woo
authors: SW
authors: Han
authors: Dal-Hee
authors: DH
authors: Min
mesh_terms: D002232:Carbocyanines / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D022022:Nuclear Pore / Q000737:chemistry*; D010316:Particle Size
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003911:Dextrans; D006046:Gold; D004317:Doxorubicin