Superior proapoptotic activity of curcumin-loaded mixed block copolymer micelles with mitochondrial targeting properties. (24th October 2018)

• Record Type: Journal Article
• Authors: Momekova, Denitsa; Ugrinova, Iva; Slavkova, Marta; Momekov, Georgi; Grancharov, Georgy; Gancheva, Valeria; Petrov, Petar D.
• Is Part Of: Biomaterials science. Volume 6:Number 12(2018)
• Page Start: 3309
• Page End: 3317
• Publication Date: 2018-10-24
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c8bm00644j
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Multifunctional micelles based on two co-assembled block copolymers are proven to effectively accumulate and deliver curcumin in mitochondria, thus, inducing a much higher proapoptotic activity than single copolymer micelles. Abstract : Targeting tumor cell mitochondria is a prospective strategy for highly effective anticancer therapy. Consequently, the development of potent systems for the targeted delivery of mitochondria-acting therapeutics to mitochondria has the potential to boost this sector of nanomedicine. In this study, a functional mixed micellar system based on two co-assembled triblock copolymers, poly(2-(dimethylamino)ethyl methacrylate)- b -poly(ε-caprolactone)- b -poly(2-(dimethylamino)ethyl methacrylate) bearing triphenylphosphonium ligands (PDMAEMA(TPP+)20- b -PCL70 - b -PDMAEMA(TPP+)20) and poly(ethylene oxide)- b -poly(ε-caprolactone)- b -poly(ethylene oxide) (PEO113 - b -PCL70 - b -PEO113 ), was assessed for the mitochondria targeted delivery of curcumin. The high proapoptotic activity of the system and the sub-cellular mechanisms of cytotoxicity were demonstrated using a chemosensitive HL-60 cell line and its resistant alternative HL-60/DOX. Next, the successful localization of nanocarriers in mitochondria was proved by fluorescence microscopy with the aid of DAPI (4′, 6-diamidino-2-phenylindole) as a cellular localization tracker. The in vitro experiments revealed the great potential of the functional system developed for the targeted delivery of curcumin to mitochondria, causing programmed tumor cell death.