Fabrication of biocleavable crosslinked polyprodrug vesicles via reversible donor–acceptor interactions for enhanced anticancer drug delivery. Issue 21 (1st May 2019)

• Record Type: Journal Article
• Authors: Zhang, Xiaolong; Hua, Qi; Meng, Ping; Wang, Mingqi; Wang, Yunfei; Sun, Lu; Ma, Liwei; Wang, Baoyan; Yu, Cuiyun; Wei, Hua
• Is Part Of: Polymer chemistry. Volume 10:Issue 21(2019)
• Page Start: 2666
• Page End: 2673
• Publication Date: 2019-05-01
• Subjects: Polymers -- Periodicals; Macromolecules -- Periodicals; Polymerization -- Periodicals; 547.705
• DOI: 10.1039/c9py00404a
• Languages: English
• ISSNs: 1759-9954

Abstract

Abstract : Reversible donor–acceptor interactions were used to prepare biocleavable crosslinked polyprodrug vesicles toward enhanced anticancer drug delivery. Abstract : Incorporation of various dynamic stimuli-responsive bonds to nanocarriers has been repeatedly highlighted to provide an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficiency; however, most of the developed systems still suffer from drug leakage-associated side effects due to insufficient stability and unsatisfactory therapeutic efficiency attributed to low drug loading capacity. To further address these critical issues, herein we reported a coordination-driven formation of biocleavable crosslinked polyprodrug vesicles (CPV) based on the reversible coordination interactions between the electron acceptor-containing polyprodrug and electron donor-based crosslinker, 1, 6-hexanediamine. The resulting CPV exhibited a high drug loading content of 34.8%, and simultaneously enhanced extracellular micelle stability and promoted intracellular redox-triggered decrosslinking and drug release. More importantly, a comparison study further revealed that the CPV outperformed the noncrosslinked analogues in terms of greater stability, faster redox-triggered decrosslinking and drug release, a more compact structure with a smaller size toward higher cellular uptake, and greater in vitro cytotoxicity. This work thus developed a robust reversible crosslinking strategy to address high stability vs . sufficient therapeutic efficiency dilemma of polyprodrug-based nanocarriers.