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

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.