Biotin-functionalized targeting anti-tumor complex based on β-cyclodextrin and methotrexate

Abstract The design and construction of tumor-targeted drug delivery systems provide us a facile method to treat cancers selectively. In this work, a biotin-targeting inclusion complex based on β-cyclodextrin and methotrexate was designed and prepared successfully. Compared with other delivery systems, in addition to hypotoxicity and high bioavailability, this targeting inclusion complex also has relatively high drug conjugation rate and with the linkage of more than 1/5 targeting ligand. In order to verify physical and chemical properties of this system, a series of experiments were carried out. The results showed that methotrexate-cyclodextrin conjugate could form very stable inclusion complex with biotin-adamantine conjugate. Water solubility of methotrexate was improved greatly by the introduction of β-cyclodextrin. In addition, according to MTT assay results, anticancer activity of amantadine-biotin/methotrexate-cyclodextrin inclusion complex against three human cancer cell lines was higher than methotrexate-cyclodextrin conjugate and free methotrexate. Further, targeting effect of the inclusion complex was also confirmed by the addition of biotin with different concentrations to make biotin receptors be saturated to vary degrees previously, which also provides a strategy for the verification of tumor-targeting of biotin. Serum stability test and drug release test also confirmed that this biotin-targeting inclusion complex was expected to be applied in the field of biomedicine for further research.