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

摘要: Resistance to platinum agents is challenging in cancer treatment with drugs. Such resistant cells prevent effective accumulation intracellular and alter cellular adaptations survive from cytotoxicity by regulating corresponding proteins expression. Ideal therapeutics should combine resolution these pump non-pump relevant resistance of achieve high efficacy low side effect. Fe3O4 nanocarrier loaded drugs could enter a more efficient endocytosis manner which circumvents pump-relevant drug resistance. EZH2 protein was previously found be over-expressed drug-resistant reported involved play vital role anti-apoptosis pathways. Here, we report nanoparticles siEZH2 (siRNA), prodrug in +4 oxidation state (cis, cis, trans-diamminedichlorodisuccinato-platinum-(IV), namely Pt(IV)) luteinizing hormone-releasing hormone (LHRH) targeting polypeptides. Results show that targeted loading synergize Pt(IV) result similar cell killing performance A2780/DDP (cisplatin resistant) compared non-siEZH2 A2780 cells sensitive). Thus, this Fe3O4@PEI-Pt(IV)-PEG-LHRH@siEZH2 reverse the cisplatin aspects, fully taking advantage system.