title: Gold nanoparticles with a monolayer of doxorubicin-conjugated amphiphilic block copolymer for tumor-targeted drug delivery.
abstract: Gold (Au) nanoparticles (NPs) stabilized with a monolayer of folate-conjugated poly(L-aspartate-doxorubicin)-b-poly(ethylene glycol) copolymer (Au-P(LA-DOX)-b-PEG-OH/FA) was synthesized as a tumor-targeted drug delivery carrier. The Au-P(LA-DOX)-b-PEG-OH/FA NPs consist of an Au core, a hydrophobic poly(l-aspartate-doxorubicin) (P(LA-DOX)) inner shell, and a hydrophilic poly(ethylene glycol) and folate-conjugated poly(ethylene glycol) outer shell (PEG-OH/FA). The anticancer drug, doxorubicin (DOX), was covalently conjugated onto the hydrophobic inner shell by acid-cleavable hydrazone linkage. The DOX loading level was determined to be 17 wt%. The Au-P(LA-DOX)-b-PEG-OH/FA NPs formed stable unimolecular micelles in aqueous solution. The size of the Au-P(LA-DOX)-b-PEG-OH/FA micelles were determined as 24-52 and 10-25 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The conjugated DOX was released from the Au-P(LA-DOX)-b-PEG-OH/FA micelles much more rapidly at pH 5.3 and 6.6 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. Cellular uptake of the Au-P(LA-DOX)-b-PEG-OH/FA micelles facilitated by the folate-receptor-mediated endocytosis process was higher than that of the micelles without folate. This was consistent with the higher cytotoxicity observed with the Au-P(LA-DOX)-b-PEG-OH/FA micelles against the 4T1 mouse mammary carcinoma cell line. These results suggest that Au-P(LA-DOX)-b-PEG-OH/FA NPs could be used as a carrier with pH-triggered drug releasing properties for tumor-targeted drug delivery.
authors.affiliation: Department of Mechanical Engineering, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
authors.forename: Mani
authors.initials: M
authors.lastname: Prabaharan
authors.forename: Jamison J
authors.initials: JJ
authors.lastname: Grailer
authors.forename: Srikanth
authors.initials: S
authors.lastname: Pilla
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
authors.forename: Shaoqin
authors.initials: S
authors.lastname: Gong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004705:Endocytosis; D005492:Folic Acid / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000737:chemistry
chemical_list: D008823:Micelles; D011108:Polymers; D006046:Gold; D004317:Doxorubicin; D005492:Folic Acid