title: Disulfide bond bridge insertion turns hydrophobic anticancer prodrugs into self-assembled nanomedicines.
abstract: It is commonly observed that hydrophobic molecules alone cannot self-assemble into stable nanoparticles, requiring amphiphilic or ionic materials to support nanoparticle stability and function in vivo. We report herein newly self-assembled nanomedicines through entirely different mechanisms. We present proof-of-concept methodology and results in support of our hypothesis that disulfide-induced nanomedicines (DSINMs) are promoted and stabilized by the insertion of a single disulfide bond into hydrophobic molecules, in order to balance the competition between intermolecular forces involved in the self-assembly of nanomedicines. This hypothesis has been explored through diverse synthetic compounds, which include four first-line chemotherapy drugs (paclitaxel, doxorubicin, fluorouracil, and gemcitabine), two small-molecule natural products and their derivatives, as well as a fluorescent probe. Such an unprecedented and highly reproducible system has the potential to serve as a synthetic platform for a wide array of safe and effective therapeutic and diagnostic nanomedicine strategies.
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Qingchuan
authors.initials: Q
authors.lastname: Zheng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: John K
authors.initials: JK
authors.lastname: Fallon
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Haynes
authors.forename: Guimei
authors.initials: G
authors.lastname: Lin
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Dun
authors.initials: D
authors.lastname: Wang
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.forename: Linxiang
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004220:Disulfides / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008958:Models, Molecular; D050997:Nanomedicine; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D005456:Fluorescent Dyes; D011355:Prodrugs
keywords: disulfide bond; nanomaterials; nanomedicines; nanoparticles; prodrug; self-assemble