Dual-sensitive nanocomposites based on poly(4-vinylpyridine-co-N-vinylcaprolactam) and copper oxide nanoparticles for controlled doxorubicin delivery

This work reports the synthesis, characterization, and evaluation of novel nanocarriers, composed of poly(4-vinylpyridine-co-N-vinylcaprolactam) coated onto copper oxide nanoparticles (CuO NPs) through free radical polymerization. First, CuO NPs were obtained by chemical precipitation and functionalized with vinyltrimethoxysilane (VS). The effects of the concentration and feed ratio of comonomers, and reaction time on grafting percentage and copolymer composition were investigated. The nanocomposites were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS) while colloidal stability, size, and pH/thermoresponsive behavior were studied by dynamic light scattering (DLS) and zeta potential (ζ). Doxorubicin (DOX) loading and release experiments were evaluated at different pH (5 and 7.4) and temperature (25 and 37 °C). In vitro cytotoxicity was assessed against breast cancer cell line (MDA-MB-231) and human fibroblasts (1132Sk) to evaluate nanocarriers anticancer potential. The CuO NPs presented semispherical morphology with an average size of 13 nm, while the nanocomposites exhibited matrix-dispersed morphology. Samples with copolymer grafting < 50% presented good colloidal stability with hydrodynamic size (Dh) ∼ 155 nm, critical pH of 5.6, and lower critical solution temperature (LCST) of 35 °C. The obtained nanocarriers were able to load and release DOX in a controlled way depending on both pH and temperature with a maximum value of 87% at pH of 5 and 37 °C. Finally, the nanocarriers exhibited an important cytotoxicity enhancement (twofold reduction of IC 50 ) against breast cancer cell line, for DOX-loaded samples, after 48 h of incubation.