Surface functionalized gold nanoparticles for drug delivery.
Gold nanoparticles have been widely explored as cancer therapeutics and diagnostic agents in recent years. With their unique subcellular size and good biocompatibility, gold nanoparticles are a promising drug delivery vehicle. In this study, folic acid-coated gold nanoparticles conjugated with fluorophore FITC through amine terminated poly(ethylene glycol) were prepared and confocal microscopy together with bright-field differential interference contrast imaging data showed that folic acid-coated gold nanoparticles accumulated mainly in cytoplasm of primary human fibroblasts, without causing any observable cytotoxicity upon exposure for 48 hours. Through the further development of a drug delivery system that conjugates doxorubicin onto the surface of gold nanoparticles with a poly(ethylene glycol) spacer via an SMCC linker, we demonstrated that multidrug resistance in cancer cells can be significantly overcome by a combination of highly efficient cellular entry and enhanced cytotoxicity of Au-SMCC-DOX nanoconjugates, as revealed both by confocal microscopy imaging and cytotoxicity assay. The prepared Au-SMCC-DOX nanoconjugates demonstrated enhanced drug accumulation and retention in multidrug resistant hepG2-R cancer cells when it was compared with free doxorubicin, with a cytoplasm accumulation profile. The results indicated that gold nanoparticles are a kind of promising drug delivery vehicle with good biocompatibility and suitable for further applications in drug delivery for improved chemotherapy, especially for overcoming multidrug resistance.
State Key Lab of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China.
Jinping
J
Cheng
Yan-Juan
YJ
Gu
Shuk Han
SH
Cheng
Wing-Tak
WT
Wong
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D008954:Models, Biological; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D013499:Surface Properties
D000970:Antineoplastic Agents; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D058726:Nanoconjugates; D011092:Polyethylene Glycols; D006046:Gold; D004317:Doxorubicin