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Chemical Design of Both a Glutathione-Sensitive Dimeric Drug Guest and a Glucose-Derived Nanocarrier Host to Achieve Enhanced Osteosarcoma Lung Metastatic Anticancer Selectivity

Although nanomedicines have been pursued for nearly 20 years, fundamental chemical strategies that seek to optimize both the drug and drug carrier together in a concerted effort remain uncommon yet may be powerful. In this work, two block polymers and one dimeric prodrug molecule were designed to be coassembled into degradable, functional nanocarriers, where the chemistry of each component was defined to accomplish important tasks. The result is a poly(ethylene glycol) (PEG)-protected redox-responsive dimeric paclitaxel (diPTX)-loaded cationic poly(d-glucose carbonate) micelle (diPTX@CPGC). These nanostructures showed tunable sizes and surface charges and displayed controlled PTX drug release profiles in the presence of reducing agents, such as glutathione (GSH) and dithiothreitol (DTT), thereby resulting in significant selectivity for killing cancer cells over healthy cells. Compared to free PTX and diPTX, diPTX@CPGC exhibited improved tumor penetration and significant inhibition of tumor cell growth tow...

Authors:   Lu Su; Richen Li; Sarosh Khan; Ryan Clanton; Fuwu Zhang; Yen-Nan Lin; Yue Song; Hai Wang; Jingwei Fan; Soleil Hernandez; Andrew S. Butters; Gamal Akabani; Ronan MacLoughlin; Justin Smolen; Karen L. Wooley
Journal:   Journal of the American Chemical Society
Year:   2018
DOI:   10.1021/jacs.7b11462
Publication date:   19-Jan-2018
Facts, background information, dossiers
  • selectivity
  • Paclitaxel
  • glutathione
  • cancer cells
More about American Chemical Society Publications
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