Mcl-1 small-molecule inhibitors encapsulated into nanoparticles exhibit increased killing efficacy towards HCMV-infected monocytes

作者：Burrer Christine M; Auburn Helen; Wang Xu; Luo Juntao; Abulwerdi Fardokht A; Nikolovska Coleska Zaneta; Chan Gary C^*

来源：Antiviral Research, 2017, 138: 40-46.

DOI：10.1016/j.antiviral.2016.11.027

• Cytomegalovirus
• Monocytes
• Myeloid cell leukemia 1
• Nanoparticles
• Small-molecule inhibitor

Human cytomegalovirus (HCMV) spreads and establishes a persistent infection within a host by stimulating the survival of carrier myeloid cells via the upregulation of Mcl-1, an antiapoptotic member of the Bcl-2 family of proteins. However, the lack of potent Mcl-1-specific inhibitors and a targetable delivery system has limited the ability to exploit Mcl-1 as a therapeutic strategy to eliminate HCMV-infected monocytes. In this study, we found a lead compound from a novel class of Mcl-1 small-molecule inhibitors rapidly induced death of HCMV-infected monocytes. Moreover, encapsulation of Mcl-1 antagonists into myeloid cell-targeting nanoparticles was able to selectively increase the delivery of inhibitors into HCMV-activated monocytes, thereby amplifying their potency. Our study demonstrates the potential use of nanotechnology to target Mcl-1 small-molecule inhibitors to HCMV-infected monocytes.

• 出版日期2017-2