Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma

Cinzia Federico, Kinan Alhallak, Jennifer Sun, Kathleen Duncan, Feda Azab, Gail P. Sudlow, Pilar Puente, Barbara Muz, Vaishali Kapoor, Luna Zhang, Fangzheng Yuan, Matea Markovic, Joseph Kotsybar, Katherine Wasden, Nicole Guenthner, Shannon Gurley, Justin King, Daniel Kohnen, Noha N. Salama, Dinesh Thotala, Dennis E. Hallahan, Ravi Vij, John F. DiPersio, Samuel Achilefu and Abdel Kareem Azab ()
Additional contact information
Cinzia Federico: Washington University School of Medicine
Kinan Alhallak: Washington University School of Medicine
Jennifer Sun: Washington University School of Medicine
Kathleen Duncan: Washington University School of Medicine
Feda Azab: Washington University School of Medicine
Gail P. Sudlow: Washington University School of Medicine
Pilar Puente: Washington University School of Medicine
Barbara Muz: Washington University School of Medicine
Vaishali Kapoor: Washington University School of Medicine
Luna Zhang: Washington University School of Medicine
Fangzheng Yuan: Washington University School of Medicine
Matea Markovic: Washington University School of Medicine
Joseph Kotsybar: Washington University School of Medicine
Katherine Wasden: Washington University School of Medicine
Nicole Guenthner: Washington University School of Medicine
Shannon Gurley: Washington University School of Medicine
Justin King: Washington University School of Medicine
Daniel Kohnen: Washington University School of Medicine
Noha N. Salama: St. Louis College of Pharmacy
Dinesh Thotala: Washington University School of Medicine
Dennis E. Hallahan: Washington University School of Medicine
Ravi Vij: Washington University School of Medicine
John F. DiPersio: Washington University School of Medicine
Samuel Achilefu: Washington University
Abdel Kareem Azab: Washington University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Drug resistance and dose-limiting toxicities are significant barriers for treatment of multiple myeloma (MM). Bone marrow microenvironment (BMME) plays a major role in drug resistance in MM. Drug delivery with targeted nanoparticles have been shown to improve specificity and efficacy and reduce toxicity. We aim to improve treatments for MM by (1) using nanoparticle delivery to enhance efficacy and reduce toxicity; (2) targeting the tumor-associated endothelium for specific delivery of the cargo to the tumor area, and (3) synchronizing the delivery of chemotherapy (bortezomib; BTZ) and BMME-disrupting agents (ROCK inhibitor) to overcome BMME-induced drug resistance. We find that targeting the BMME with P-selectin glycoprotein ligand-1 (PSGL-1)-targeted BTZ and ROCK inhibitor-loaded liposomes is more effective than free drugs, non-targeted liposomes, and single-agent controls and reduces severe BTZ-associated side effects. These results support the use of PSGL-1-targeted multi-drug and even non-targeted liposomal BTZ formulations for the enhancement of patient outcome in MM.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19932-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19932-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19932-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().