title: A unique highly hydrophobic anticancer prodrug self-assembled nanomedicine for cancer therapy.
abstract: In contrast with common thought, we generated highly hydrophobic anticancer prodrug self-assembled nanoparticles without the aid of surface active substances, based on the conjugation of docetaxel to d-α-tocopherol succinate. The reduction-sensitive prodrug was synthesized with a disulfide bond inserted into the linker and was compared with a control reduction-insensitive prodrug. The morphology and stability of self-assembled nanoparticles were investigated. Cytotoxicity and apoptosis assays showed that the reduction-sensitive nanoparticles had higher anticancer activity than the reduction-insensitive nanoparticles. The reduction-sensitive nanoparticles exhibited favorable in vivo antitumor activity and tolerance compared with docetaxel Tween80-containing formulation and the reduction-insensitive nanoparticles. Taken together, the unique nanomedicine demonstrated a number of advantages: (i) ease and reproducibility of preparation, (ii) high drug payload, (iii) superior stability, (iv) prolonged circulation, and (v) improved therapeutic effect. This highly reproducible molecular assembly strategy should motivate the development of new nanomedicines.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; School of Pharmacy, Shanxi Medical University, Shanxi, China.
authors.forename: Guolian
authors.initials: G
authors.lastname: Ren
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Mengjuan
authors.initials: M
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: wangyjspu@163.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, China. Electronic address: chbyxl@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D050997:Nanomedicine; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs
keywords: Disulfide bond; Docetaxel; Nanomedicine; Prodrug; Self-assemble