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Facile Fabrication of Tumor Redox‐Sensitive Nanoassemblies of Small‐Molecule Oleate Prodrug as Potent Chemotherapeutic Nanomedicine
Author(s) -
Luo Cong,
Sun Jin,
Sun Bingjun,
Liu Dan,
Miao Lei,
Goodwin Tyler Jay,
Huang Leaf,
He Zhonggui
Publication year - 2016
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201601597
Subject(s) - prodrug , nanomedicine , conjugate , biodistribution , chemistry , in vivo , small molecule , paclitaxel , drug , pharmacology , nanotechnology , oleic acid , combinatorial chemistry , in vitro , cancer , materials science , biochemistry , medicine , nanoparticle , biology , mathematical analysis , mathematics , microbiology and biotechnology
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.