title: Sensitizing cancer cells to TRAIL-induced death by micellar delivery of mitoxantrone.
abstract: TNFα-related apoptosis-inducing ligand (TRAIL) induces death selectively in cancer cells. However, subpopulations of cancer cells are either resistant to or can develop resistance to TRAIL-induced death. As a result, strategies that overcome this resistance are currently under investigation. We have recently identified several US FDA-approved drugs with TRAIL-sensitization activity against prostate, breast and pancreatic cancer cells. Mitoxantrone, a previously unknown TRAIL sensitizer identified in the screen, was successfully encapsulated in methoxy-, amine- and carboxyl-terminated PEG-DSPE micelles in order to facilitate delivery of the drug to cancer cells. All three micelle types were extensively characterized for their physicochemical properties and evaluated for their ability to sensitize cancer cells to TRAIL-induced death. Our results indicate that micelle-encapsulated mitoxantrone can be advantageously employed in synergistic treatments with TRAIL, leading to a biocompatible delivery system and amplified cell killing activity for combination chemotherapeutic cancer treatments.
authors.affiliation: Harrington Biomedical Engineering, Arizona State University, Tempe, AZ 85287, USA. kaushal.rege@asu.edu.
authors.forename: Taraka Sai Pavan
authors.initials: TS
authors.lastname: Grandhi
authors.forename: Thrimoorthy
authors.initials: T
authors.lastname: Potta
authors.forename: David J
authors.initials: DJ
authors.lastname: Taylor
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Tian
authors.forename: Roger H
authors.initials: RH
authors.lastname: Johnson
authors.forename: Deirdre R
authors.initials: DR
authors.lastname: Meldrum
authors.forename: Kaushal
authors.initials: K
authors.lastname: Rege
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004355:Drug Stability; D004357:Drug Synergism; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008823:Micelles; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D050997:Nanomedicine; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013053:Spectrophotometry; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D010714:Phosphatidylethanolamines; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D008942:Mitoxantrone
keywords: PEG-DSPE micelles; TRAIL; combination treatment; mitoxantrone