New diamidequat-type surfactants in fabrication of long-sustained theranostic nanocapsules: Colloidal stability, drug delivery and bioimaging

摘要

We report a new theranostic nanoformulation to transport both chemotherapeutic and imaging agents for successfully exterminating cancer cells. This strategy is based on encapsulation of colchicine (cytostatic drug) and coumarin-6 (fluorescent biomarker) in oil-core nanocarriers stabilized by diamidequat-type surfactants - N,N-dimethyl-N,N-bis[2-(N-alkylcarbamoyl) ethyl]ammonium methylsulfates (2xC(n)A-MS, n= 8,10,12), and fabricated by the nanoprecipitation technique. The surfactants were synthesized using a technologically viable methodology and characterized. The potential of the encapsulated theranostic cargoes was evaluated in cytotoxicity studies as well as in imaging of intracellular localization, accumulation and distribution of cargoes delivered to well characterized human cancer cell lines - doxorubicin-sensitive breast (MCF-7/VVT), alveolar basal epithelial (A549) and skin melanoma (MEWO) - performed by confocal laser scanning microscopy (CLSM). Backscattered profiles obtained by the turbidimetric technique were applied to evaluate physical stability of the obtained nanosystems. DLS measurements confirmed the particle diameter to be below 200 nm, while AFM - its morphology and shape. Doppler electrophoresis provided a highly positive zeta-potential. UV-vis was applied to determine the encapsulation efficiencies (ca. 90%), and release profiles. The study demonstrates that the soft cationic diamidequat-type surfactants are suitable for the stabilization of theranostic nanodispersions, and they can constitute a new functional class of stabilizers of nanoparticles and have a progressive impact onto development of formulations. Furthermore, our results demonstrate excellent biocompatibility of the studied long-sustained monodisperse oil-core nanocapsules, stabilized by 2xC(n)A-MS, which makes them promising for cell imaging. (C) 2015 Elsevier B.V. All rights reserved.