The novel platinum(IV) prodrug with self-assembly property and structure-transformable character against triple-negative breast cancer. (February 2020)

• Record Type: Journal Article
• Authors: Yang, Conglian; Tu, Kun; Gao, Hanlu; Zhang, Liao; Sun, Yu; Yang, Ting; Kong, Li; Ouyang, Defang; Zhang, Zhiping
• Is Part Of: Biomaterials. Volume 232(2020)
• Publication Date: 2020-02
• Subjects: Platinum(IV) prodrug -- Adjudin -- Self-assembly -- Structure transform -- Drug resistance -- Triple-negative breast cancer; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2019.119751
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Herein, a small library of Pt(IV) prodrugs based on cisplatin and chemosensitizer adjudin (ADD) were explored for efficient cisplatin resistant triple-negative breast cancer (TNBC) treatment. We further elucidated the detail relationship of chemical structure, alkyl chain length (ethyl to dodecyl) and ADD substituted degree, with respect to the self-assembly ability and cytotoxic effect of prodrugs. It demonstrated that all prodrugs could self-assemble into nanomedicine, which was in consist with the molecule structure building and self-assembly simulation. All nanomedicines possessed small particle size, uniform morphology and ultra-high drug loading content (84.0%–86.5%). Moreover, the length of alkyl chain was of great importance for the structure-transformable character and cytotoxicity of nanomedicines. Interestingly, ADD monosubstituted with butyl or hexyl contralateral substituted prodrug (C4 -Pt-ADD or C6 -Pt-ADD) assembled nanomedicine could convert to wire or sheet structure. These transformable nanoparticles showed great potential in improving the sensitivity of cisplatin to TNBC with up to 266-fold lower IC50 value and significantly enhanced in vivo tumor growth inhibition. Therefore, the self-assembled nanomedicine based on Pt(IV)-ADD could be a promising strategy for TNBC therapy. Graphical abstract: A series of self-assembled nanomedicine based on Pt(IV)-ADD prodrug were fabricated here for cisplatin resistant triple-negative breast cancer (TNBC) therapy. Interestingly, the length of alkyl chain was of great importance for the structure-transformable character and cytotoxicity of nanomedicines. ADD monosubstituted with butyl or hexyl contralateral substituted prodrug (C4 -Pt-ADD or C6 -Pt-ADD) assembled nanomedicine could convert to wire or sheet structure. These transformable nanoparticles showed great potential in improving cisplatin sensitive to TNBC with up to 266-fold lower IC50 value and significantly enhanced in vivo tumor growth inhibition. Image 1 Highlights: A series of self-assembled nanomedicine based on Pt(IV)-ADD prodrug were developed. The introduction of ADD endowed the prodrugs with self-assembly ability. The length of alkyl chain was of great importance for structure-transformable character and cytotoxicity of nanomedicines. C4 -Pt-ADD or C6 -Pt-ADD prodrug assembled nanomedicine could convert to wire or sheet structure. These structure-transformable nanoparticles showed great potential in improving cisplatin sensitive to TNBC.