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

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.

Complex Formation Between Lysozyme and Stabilized Micelles with a Mixed Poly(ethylene oxide)/Poly(acrylic acid) Shell.

The electrostatic complexation between lysozyme and stabilized polymeric micelles (SPMs) with a poly(acrylic acid) (PAA) or a mixed poly(ethylene oxide)/poly(acrylic acid) (PEO/PAA) shell (SPMs with a mixed shell, SPMMS) and a temperature-responsive poly(propylene oxide) (PPO) core was investigated by means of dynamic, static, and electrophoretic light scattering. The SPMs and different types of SPMMS used resulted from the self-assembly of PAA-PPO-PAA triblock copolymer chains, or PAA-PPO-PAA and PEO-PPO-PEO triblock copolymer chain mixtures (with varying chain lengths and molar ratios) in aqueous solutions at pH 10 and the subsequent cross-linking of their PPO cores via loading and photo-cross-linking of pentaerythritol tetraacrylate (PETA). The solution behavior, structure and properties of the formed complexes at pH 7 and 0.01 M ionic strength, were studied as a function of the protein concentration in the solution (the concentration of the stabilized micelles was kept constant) or equivalently the ratio of the two components. The complexation process and properties of the complexes proved to be dependent on the protein concentration, while of particular interest was the effect of the structure of the shell of the SPMs on the stability/solubility of the complexes. Finally, the fluorescence and mid infrared spectroscopic investigation of the structure of the complexed protein showed that, although a small stretching of the protein molecules occurred in some cases, no protein denaturation takes place upon complexation.