Facile Fabrication of Tumor Redox‐Sensitive Nanoassemblies of Small‐Molecule Oleate Prodrug as Potent Chemotherapeutic Nanomedicine |
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| Authors: | Cong Luo Jin Sun Bingjun Sun Dan Liu Lei Miao Tyler Jay Goodwin Leaf Huang Zhonggui He |
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| Affiliation: | 1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China;2. Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China;3. Key Laboratory of Structure‐Based Drug Design and Discovery, Shenyang Pharmaceutical University, Shenyang, P. R. China;4. Division of Molecular Pharmaceutics and Center of Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA |
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| Abstract: | The conjugate of paclitaxel (PTX) and docosahexaenoic acid has entered into clinical trials. However, the most recent clinical outcomes fell short of expectations, due to the extremely slow drug release from the hydrophobic conjugates. Herein, a novel prodrug‐based nanoplatform self‐assembled by the disulfide bond linked conjugates of PTX and oleic acid for rapid and differential release of PTX in tumor cells is reported. This redox‐responsive prodrug‐nanosystem demonstrates multiple therapeutic advantages, including one‐step facile fabrication, high drug‐loading efficiency (56%, w/w), on‐demand drug release responding to redox stimuli, as well as favorable cellular uptake and biodistribution. These advantages result in significantly enhanced antitumor efficacy in vivo, with the tumor almost completely disappearing in mice. Such a uniquely engineered prodrug‐nanosystem has great potential to be used as potent chemotherapeutic nanomedicine in clinical cancer therapy. |
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| Keywords: | cancer therapy disulfide bonds oleate prodrugs paclitaxel prodrug‐nanosystems |
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