Abstract
In order to achieve efficient delivery of methotrexate (MTX), thymine-chitosan nanoparticles (Thy-Cs NPs) were prepared, and further decorated with lactobionic acid (LA) to obtain tumor-targeting nanoparticles (LA-Thy-Cs NPs). These nanoparticles possessed a regular spherical structure with the average size about 190–250 nm and narrow size distribution, which were kinetically stable in the physiological environment. Due to electrostatic interactions and multiple hydrogen-bonding interactions between MTX and carriers, MTX was loaded into Thy-Cs NPs with high drug loading content (~20%). MTX release from Thy-Cs NPs was significantly accelerated in the mildly acidic environment due to the destruction of two types of non-covalent interactions. In vitro cell experiments demonstrated that LA-Thy-Cs NPs could be efficiently internalized into hepatoma carcinoma cells, leading to higher cytotoxicity. Moreover, MTX-loaded LA-Thy-Cs NPs performed an enhanced growth inhibition in three-dimensional multicellular tumor spheroids. Thus, the LA decorated thymine-chitosan nanocarriers can be a promising candidate for efficient delivery of MTX.
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