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ACS Nano. 2011 Sep 27;5(9):6962-70. doi: 10.1021/nn201446c. Epub 2011 Aug 12.

Strategy for increasing drug solubility and efficacy through covalent attachment to polyvalent DNA-nanoparticle conjugates.

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Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.


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.

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