title: Strategy for increasing drug solubility and efficacy through covalent attachment to polyvalent DNA-nanoparticle conjugates.
abstract: Paclitaxel, a potent chemotherapeutic utilized in a variety of cancers, can be limited in its effectiveness due to inherent insolubility in aqueous media and acquired chemoresistance within certain cells. An approach has been developed for increasing Paclitaxel solubility and effectiveness by covalent attachment to gold nanoparticles via DNA linkers. The resulting conjugates are highly soluble in aqueous buffer, exhibiting greater than a 50-fold increase in solubility over the unconjugated drug. DNA linkers are labeled with a fluorophore, which affords a convenient means of visualizing resultant conjugates within cells. Internalized conjugates demonstrate increased activity as compared with free drug across a variety of cell types, including a Paclitaxel-resistant cell line. Attachment to DNA-nanoparticle conjugates may become a general strategy for solubilizing and enhancing a wide variety of therapeutic agents in aqueous media.
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Xu
authors.forename: Robert
authors.initials: R
authors.lastname: Lam
authors.forename: David
authors.initials: D
authors.lastname: Giljohann
authors.forename: Dean
authors.initials: D
authors.lastname: Ho
authors.forename: Chad A
authors.initials: CA
authors.lastname: Mirkin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D006801:Humans; D020287:In Situ Nick-End Labeling; D053768:Metal Nanoparticles; D017239:Paclitaxel / Q000737:chemistry*; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005456:Fluorescent Dyes; D006046:Gold; D004247:DNA; D017239:Paclitaxel