Liposomal carfilzomib nanoparticles effectively target multiple myeloma cells and demonstrate enhanced efficacy in vivo

Jonathan D. Ashley, Jared F. Stefanick, Valerie A. Schroeder, Mark A. Suckow, Nathan J. Alves, Rikio Suzuki, Shohei Kikuchi, Teru Hideshima, Kenneth C. Anderson, Tanyel Kiziltepe, Basar Bilgicer

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Carfilzomib, a recently FDA-approved proteasome inhibitor, has remarkable anti-myeloma (MM) activity. However, its effectiveness is limited by associated severe side-effects, short circulation half-life, and limited solubility. Here, we report the engineering of liposomal carfilzomib nanoparticles to overcome these problems and enhance the therapeutic efficacy of carfilzomib by increasing tumoral drug accumulation while decreasing systemic toxicity. In our design, carfilzomib was loaded into the bilayer of liposomes to yield stable and reproducible liposomal nanoparticles. Liposomal carfilzomib nanoparticles were efficiently taken up by MM cells, demonstrated proteasome inhibition, induced apoptosis, and exhibited enhanced cytotoxicity against MM cells. In vivo, liposomal carfilzomib demonstrated significant tumor growth inhibition and dramatically reduced overall systemic toxicity compared to free carfilzomib. Finally, liposomal carfilzomib demonstrated enhanced synergy in combination with doxorubicin. Taken together, this study establishes the successful synthesis of liposomal carfilzomib nanoparticles that demonstrates improved therapeutic index and the potential to improve patient outcome in MM.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalJournal of Controlled Release
StatePublished - Dec 28 2014

Bibliographical note

Funding Information:
We thank the Notre Dame Integrated Imaging Facility for confocal microscopy, the Center for Environmental Science and Technology for the use of DLS, and the Mass Spectrometry and Proteomics Facility for the use of MALDI-TOF-MS. We thank Deborah Donahue and the WM Keck Center for the irradiation of the mice. This work was supported by the Hollis Brownstein Research Program Grant from Leukemia Research Foundation .

Publisher Copyright:
© 2014 Elsevier B.V.


  • Carfilzomib
  • Liposome
  • Multiple myeloma
  • Nanoparticle
  • Proteasome inhibitor


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