Medical College of Wisconsin
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Sensitizing cancer cells to TRAIL-induced death by micellar delivery of mitoxantrone. Nanomedicine (Lond) 2014;9(12):1775-88

Date

11/08/2013

Pubmed ID

24195660

DOI

10.2217/nnm.13.125

Scopus ID

2-s2.0-84908222476   5 Citations

Abstract

TNF╬▒-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.

Author List

Grandhi TS, Potta T, Taylor DJ, Tian Y, Johnson RH, Meldrum DR, Rege K

Author

Roger H. Johnson PhD Associate Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents
Breast Neoplasms
Cell Line, Tumor
Drug Delivery Systems
Drug Stability
Drug Synergism
Female
Humans
Magnetic Resonance Spectroscopy
Male
Micelles
Mitoxantrone
Nanomedicine
Nanotechnology
Neoplasms
Phosphatidylethanolamines
Polyethylene Glycols
Prostatic Neoplasms
Spectrophotometry
TNF-Related Apoptosis-Inducing Ligand