Coordination self-assembly of platinum-bisphosphonate polymer-metal complex nanoparticles for cisplatin delivery and effective cancer therapyElectronic supplementary information (ESI) available. See DOI: 10.1039/c7nr02662e

Cisplatin (CDDP) is a potent anti-carcinogen that is widely used for various solid tumors; however, its clinical application is limited by its severe nephrotoxicity. Novel platinum-bisphosphonate polymer-metal complex nanoparticles (Pt-bp NPs), based on platinum-bisphosphonate coordination, have been established. Three polymer carriers bearing alendronate (ALN) ligands, while containing different lengths of alkyl hydrophobic chains, were synthesized. Their structures were characterized by 1 H NMR, 31 P NMR and FTIR. The ALN was used to coordinate to the CDDP precursor [Pt(NH 3 ) 2 (OSO 3 )(OH 2 )], and the Pt-bp NPs were formed spontaneously. The Pt-bp NPs formed by the polymer carrier, ALN-PEG 2k -ASA C18 , which contained the poly(ethylene glycol) chain with ALN on one side and the octadecyl hydrophobic chain on the other side, was denoted as ALN-ASA C18 -CDDP; its diameter was within 200 nm. CDDP was released in a Cl − or pH-dependent manner. The cytotoxic effects to the HeLa, A549 and MCF-7 cell lines were relatively weak, compared to CDDP. However, ALN-ASA C18 -CDDP showed significantly prolonged blood circulation time and tumor accumulation of platinum of 2.5-fold, compared to CDDP at 8 h. Besides, ALN-ASA C18 -CDDP was demonstrated to remarkably reduce systemic toxicity without compromising in vivo antitumor activity. These results indicate that the facilely prepared ALN-ASA C18 -CDDP has great utilization potential for CDDP delivery in a clinical setting. The constructed nanoparticles showed reduced systemic toxicity of cisplatin (CDDP) without compromising its in vivo antitumor activity.