New Diamidequat-type Surfactants in Fabrication of Long-sustained Theranostic Nnanocapsules: Colloidal Stability and Bioimaging

There is increasing interest in development of theranostic nanoparticles that can be applied to transport separately hydrophobic pharmaceuticals (mainly cytostatics for the cancer therapy) as well as imaging agents (organic dyes, fluorescent proteins orfluorescent semiconductor nanocrystals) to the site of disease.

Thus, we have now focused on encapsulation of colchicine (cytostatic drug) and coumarin-6 (fluorescent biomarker) in the oil-core nanocarriers, stabilized by diamidequat-type surfactants and fabricated by the emulsification/solvent-evaporation technique. The titular surfactants, N,N-dimethyl-N,N-bis[3-(alkylamido)ethyl]ammonium methylsulfates (2xC_nA-MS, n=8,10), were synthesized in a technologically convenient three step reaction. In the first step, methyl acrylate was converted in a reaction with methylamine to N-methyl-N,N-bis[2-(methyloxycarbonyl)ethyl]amine (2xC₁E). Then, in reaction of 2xC₁E with n-alkyl amine, N-methyl-N,N-bis[3-(alkylamido)ethyl]amines (2xC_nA, n = 8,10) were achieved. Finally, by quaternization with dimethylsulfate, 2xC_nA-MS (n=8,10)were produced.

The potential of the encapsulated theranostic cargoes was evaluated in cytotoxicity studies as well as in imaging of intracellular localization, accumulation and distribution of cargos delivered to well characterized human cancer cell lines - doxorubicin-sensitive breast (MCF-7/WT), alveolar basal epithelial (A549) and skin melanoma (MEWO) - performed by confocal laser scanning microscopy (CLSM). DLS measurements confirmed the particle diameter below 200 nm, while AFM and SEM - its morphology and shape. Doppler electrophoresis provided a highly positive ζ-potential. UV-Vis was applied to determine the encapsulation efficiencies (ca. 90%), and release profiles.