Targeted iron nanoparticles with platinum-(IV) prodrugs and anti-EZH2 siRNA show great synergy in combating drug resistance in  vitro and in vivo.

Targeted iron nanoparticles with platinum-(IV) prodrugs and anti-EZH2 siRNA show great synergy in combating drug resistance in vitro and in vivo. Biomaterials. 2017 Nov 14;155:112-123 Authors: Yu C, Ding B, Zhang X, Deng X, Deng K, Cheng Z, Xing B, Jin D, Ma P, Lin J Abstract Resistance to platinum agents is challenging in cancer treatment with platinum drugs. Such resistant cells prevent effective platinum accumulation intracellular and alter cellular adaptations to survive from cytotoxicity by regulating corresponding proteins expression. Ideal therapeutics should combine resolution to these pump and non-pump relevant resistance of cancer cells to achieve high efficacy and low side effect. Fe3O4 nanocarrier loaded with drugs could enter cells in a more efficient endocytosis manner which circumvents pump-relevant drug resistance. EZH2 protein which was previously found to be over-expressed in drug-resistant cancer cells was reported to be involved in platinum drug resistance and play a vital role in anti-apoptosis pathways. Here, we report Fe3O4 nanoparticles loaded with siEZH2 (siRNA), a platinum prodrug in +4 oxidation state (cis, cis, trans-diamminedichlorodisuccinato-platinum-(IV), namely Pt(IV)) and luteinizing hormone-releasing hormone (LHRH) targeting polypeptides. Results show that targeted nanoparticles loading with siEZH2 synergize with Pt(IV) and result in similar cell killing performance to A2780/DDP cells (cisplatin ...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research