Fabrication of 5-fluorouracil loaded multi-responsive molecularly imprinted poly (NVCL-co-MAA) coated black titanium dioxide nanocomposite as a chemo-photodynamic therapy agent

Abstract

TiO2 nanoparticles (NPs) are commonly used in cancer photodynamic therapy due to their ultraviolet light–triggered properties. In this study, a molecularly imprinted polymer (MIP)-coated black TiO2 (b-TiO2) nanocomposites (NCs) were synthesized using free radical polymerization of thermosensitive N-vinyl caprolactam and pH-sensitive methacrylic acid functional monomers on the surface of b-TiO2 NPs. B-TiO2 NPs were prepared using calcination of as-synthesized white TiO2 NPs (w-TiO2) at high temperatures. The MIP layer was in-situ deposited on surface-activated b-TiO2 NPs with azobisisobutyronitrile as an initiator and uracil as a pseudo-template molecule of 5-Fluorouracil (5-FU). The samples were characterized using FTIR, NIR, XRD, DLS, TEM, BET and TGA analyses. The average crystallite sizes of w-TiO2, b-TiO2 NPs and the NCs were determined through Sharer's equation as 6.8, 10.36 and 12.61 nm, respectively, which were smaller than those obtained by DLS (7.5, 115 and 130.6 nm, respectively), indicating the aggregation of small particles during calcination at high temperatures. The equilibrium adsorption capacity of NCs and non-imprinted NCs with specific areas of 14.80 m2.g−1 and 7.611 m2.g−1, respectively, toward 5-FU was determined to be 80 and 25 mg.g−1, respectively, indicating that the imprinting process is highly efficient. Higher cumulative drug released in pH 5.5 and 41 ºC confirmed the remarkable potential of NCs as a pH/temperature-responsive delivery vehicle. Moreover, the NCs demonstrated enhanced photothermal/photodynamic and low hemolytic activity (< 5%) compared to b-TiO2 NPs. The findings indicate that NCs showed excellent potential for combining stimuli-responsive chemotherapy with photothermal/photodynamic therapy for melanoma treatment.