title: Fe3O4 nanoparticles with daunorubicin induce apoptosis through caspase 8-PARP pathway and inhibit K562 leukemia cell-induced tumor growth in vivo.
abstract: Nanomaterials can enhance the delivery and treatment efficiency of anticancer drugs, but the mechanisms of the tumor-reducing activity of ferrous-ferric oxide (Fe(3)O(4)) nanoparticles (NPs) with daunorubicin (DNR) have not been established. Here we investigate the synergistic effects of Fe(3)O(4) NPs with DNR on the induction of apoptosis using K562 leukemia cells. Fe(3)O(4) NPs increased the ability of DNR to induce apoptosis in both adriamycin-sensitive and adriamycin-resistant K562 cells through the caspase 8-poly(ADP-ribose) polymerase pathway. Fe(3)O(4) NPs combined with DNR also effectively inhibited the tumor growth induced by the inoculation of K562 cells into nude mice. The increased cell apoptotic rate was closely correlated with the enhanced inhibition of tumor growth. Biodistribution studies in xenograft tumors indicated that Fe(3)O(4) NPs could be potentially excreted from the body via the gastrointestinal system. In conclusion, our study suggests that Fe(3)O(4) NPs combined with anticancer drugs could serve as a better alternative for targeted therapeutic approaches to cancer treatments.
authors.affiliation: State Key Lab of Bioelectronics (Chien-Shiung Wu Lab), Department of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
authors.forename: Gen
authors.initials: G
authors.lastname: Zhang
authors.forename: Bin Bin
authors.initials: BB
authors.lastname: Lai
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Zhou
authors.forename: Bao An
authors.initials: BA
authors.lastname: Chen
authors.forename: Xue Mei
authors.initials: XM
authors.lastname: Wang
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000187:drug effects / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D005296:Ferrous Compounds / Q000737:chemistry*; D006801:Humans; D020014:K562 Cells; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D053858:Metabolic Networks and Pathways; D051379:Mice; D008819:Mice, Nude; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D005296:Ferrous Compounds; D058185:Magnetite Nanoparticles; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; D053181:Caspase 8; C034236:ferrous oxide; D003630:Daunorubicin