A Carrier-Free Nanostructure Based on Platinum(IV) Prodrug Enhances Cellular Uptake and Cytotoxicity.

['Tan J', 'Li C', 'Wang Q', 'Li S', 'Chen S', 'Zhang J', 'Wang PC', 'Ren L', 'Liang XJ']
Mol Pharm. 2018 Mar 14. doi: 10.1021/acs.molpharmaceut.8b00070. [Epub ahead of print]

Author information
['Department of Biomaterials, Key Laboratory of Biomedical Engineering of Fujian Province, College of Materials , Xiamen University , Xiamen 361005 , P. R. China.', 'Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety , National Center for Nanoscience and Technology , Beijing 100190 , P. R. China.', 'School of Life Sciences , Peking University , Beijing 100871 , P. R. China.', 'College of Chemistry & Environmental Science , Hebei University , Baoding 071002 , P. R. China.', 'Department of Radiology , Howard University , Washington , D.C. 20060 , United States.']

['Flurbiprofen, a hydrophobic COX inhibitor, was coordinated axially with oxoplatin to form a new conjugate, cis, cis, trans-[Pt(IV)(NH3)2Cl2(flurbiprofen)2]. The successful synthesis of this new conjugate was confirmed by 1H, 13C, and 195Pt NMR. The potential of this conjugate being reduced to cisplatin and subsequently exerting its DNA cross-linking ability was verified using cyclic voltammetry (CV), HPLC, and mass spectrometry (MS). This conjugate showed markedly higher cytotoxicity on many cancer cell lines than cisplatin, flurbiprofen, and their physical mixture (mole ratio, cisplatin:flurbiprofen = 1:2). This is consistent with the result of an apoptosis-inducing assay. This conjugate spontaneously assembles carrier-free nanoparticles in aqueous solution, which is confirmed by DLS, TEM, SEM, and AFM, and thus facilitates cellular uptake and markedly improves its cytotoxicity and apoptosis-inducing ability in vitro.']