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Superior proapoptotic activity of curcumin-loaded mixed block copolymer micelles with mitochondrial targeting properties

Abstract

Targeting tumor cell mitochondria is a perspective strategy for highly effective anticancer therapy. Consequently, the development of potent systems for targeted delivery of mitochondria-acting therapeutics to the site of 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 (PDMAEMA20(TPP+)-b-PCL70-b-PDMAEMA20(TPP+)) and poly(ethylene oxide)-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO113-b-PCL70-b-PEO113), was assessed for mitochondria targeted delivery of curcumin. The high proapoptotic activity of the system and the sub-cellular mechanisms of cytotoxicity were demonstrated using chemosensitive HL-60 cell line and its resistant variant HL-60/DOX. Next, the successful localization of nanocarriers in mitochondria was proven 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 developed functional system for targeted delivery of curcumin in mitochondria, causing programmed tumor cell death.

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Publication details

The article was received on 11 Jun 2018, accepted on 05 Oct 2018 and first published on 08 Oct 2018


Article type: Paper
DOI: 10.1039/C8BM00644J
Citation: Biomater. Sci., 2018, Accepted Manuscript
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    Superior proapoptotic activity of curcumin-loaded mixed block copolymer micelles with mitochondrial targeting properties

    D. Momekova, I. Ugrinova, M. Slavkova, G. Momekov, G. Grancharov, V. Gancheva and P. Petrov, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C8BM00644J

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