کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5551862 | 1557805 | 2017 | 7 صفحه PDF | دانلود رایگان |
- Mcl-1 inhibitors stimulate death of HCMV-infected monocytes.
- HCMV-infected monocytes exhibit enhanced uptake of nanoparticles.
- Encapsulated Mcl-1 inhibitors induce more potent killing of infected monocytes.
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.
Journal: Antiviral Research - Volume 138, February 2017, Pages 40-46