Facile Fabrication of Tumor Redox-Sensitive Nanoassemblies of Small-Molecule Oleate Prodrug as Potent Chemotherapeutic Nanomedicine.
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.
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
Cong
C
Luo
Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
Jin
J
Sun
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
Bingjun
B
Sun
Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
Dan
D
Liu
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, 27599, USA.
Lei
L
Miao
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, 27599, USA.
Tyler Jay
TJ
Goodwin
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, 27599, USA.
Leaf
L
Huang
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
Zhonggui
Z
He
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008819:Mice, Nude; D050997:Nanomedicine / Q000379:methods*; D019301:Oleic Acid / Q000737:chemistry*; D010084:Oxidation-Reduction; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D011355:Prodrugs; D019301:Oleic Acid; D017239:Paclitaxel
cancer therapy; disulfide bonds; oleate prodrugs; paclitaxel; prodrug-nanosystems
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