Next Article in Journal
Amorphous Nanoparticulate Formulation of Sirolimus and Its Tablets
Next Article in Special Issue
Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies
Previous Article in Journal
Iontophoretic Transdermal Delivery of Human Growth Hormone (hGH) and the Combination Effect of a New Type Microneedle, Tappy Tok Tok®
Previous Article in Special Issue
Scaffolds as Structural Tools for Bone-Targeted Drug Delivery
Article Menu
Issue 3 (September) cover image

Export Article

Open AccessFeature PaperArticle
Pharmaceutics 2018, 10(3), 154;

Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in Mice

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Box 626, 601 Elmwood Ave, Rochester, NY 14642, USA
Institute of Stomatology, Nanjing Medical University, Jiangsu Key Laboratory of Oral Diseases, Nanjing 210029, China
Department of Chemistry, University of Rochester, P.O. Box 270216, Rochester, NY 14627-0216, USA
Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14627-0216, USA
BioVinc, Pasadena, CA 91107, USA
Department of Cell Systems & Anatomy, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Received: 3 August 2018 / Revised: 29 August 2018 / Accepted: 2 September 2018 / Published: 10 September 2018
(This article belongs to the Special Issue Bone Targeted Drug Delivery)
Full-Text   |   PDF [1626 KB, uploaded 10 September 2018]   |  


Multiple myeloma (MM) is the most common cancer affecting the bone and bone marrow and remains incurable for most patients; novel therapies are therefore needed. Bortezomib (Btz) is an FDA-approved drug for the treatment of patients with MM. However, its severe side effects require a dose reduction or the potential discontinuation of treatment. To overcome this limitation, we conjugated Btz to a bisphosphonate (BP) residue lacking anti-osteoclastic activity using a novel chemical linker and generated a new bone-targeted Btz-based (BP-Btz) proteasome inhibitor. We demonstrated that BP-Btz, but not Btz, bound to bone slices and inhibited the growth of MM cells in vitro. In a mouse model of MM, BP-Btz more effectively reduced tumor burden and bone loss with less systemic side effects than Btz. Thus, BP-Btz may represent a novel therapeutic approach to treat patients with MM. View Full-Text
Keywords: drug delivery; bortezomib; velcade; bone targeting; multiple myeloma drug delivery; bortezomib; velcade; bone targeting; multiple myeloma

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Wang, H.; Xiao, L.; Tao, J.; Srinivasan, V.; Boyce, B.F.; Ebetino, F.H.; Oyajobi, B.O.; Boeckman, R.K., Jr.; Xing, L. Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in Mice. Pharmaceutics 2018, 10, 154.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top