Journal
CARBOHYDRATE RESEARCH
Volume 501, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carres.2021.108275
Keywords
Thymine-conjugated chitosan; Methotrexate; Electrostatic interaction; Multiple hydrogen-bonding interaction; Tumor-targeting
Funding
- National Natural Science Foundation of China [51603001, 81870307, 81570376]
- University Special Innovative Research Program of Department of Education of Guangdong Province [2017KTSCX189]
- National Key Research and Development Program [2018YFA0902702]
- National Science and Technology Major Project [2018ZX10731301-003-007]
- Program of Department of Education of Zhejiang Province [Y201327376]
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Lactobionic acid decorated thymine-chitosan nanoparticles showed efficient delivery of MTX, leading to higher cytotoxicity in hepatoma carcinoma cells and enhanced growth inhibition in three-dimensional multicellular tumor spheroids. These nanocarriers have promising potential for MTX delivery.
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 (similar to 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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