Guandinium Supramolecular Nanomicelles As Drug Delivery System In Breast Cancer

The guanidinium group has excellent cell membrane penetration ability,biological macromolecule adhesion ability,and potential antitumor drug activity.Polycationic carriers constructed with guanidinium groups have been widely used for gene and protein delivery.In this thesis,a new class of guanidinium-based supramolecular carrier was synthesized and used for the treatment of breast cancer.In the first part,we synthesized two adamantine guanidine compounds:ADMET and ADGUA,The structure of ADGUA and ADMET have confirmed through various physicochemical characterizations.In vitro experiments showed that both ADMET and ADGUA have anti-tumor activities that can promote cell apoptosis and induce ATP depletion in breast cancer cells.In the second part,a host-guest self-assembled supermolecular poly:mer(PCMET)was constructed in which PC as the host and ADMET as the guest.The supramolecular polymer has cytotoxicity to breast cancer cells,and the PCMET nanomicelles could efficiently deliver siRNA into the cells.Further investigation studied anti-breast cancer abilities.The PMC/siCD146 nanomicelles were constructed by carrying siCD146 siRNA with cationic polymer PCMET and chondroitin sulfate.By the introduction of chondroitin sulfate,the surface charge of nanomicelles is effectively reduced,and endocytosis in breast cancer cells,which is of high expression CD44,is increased.Under the synergistic effect of siCD146 and ADMET,the nanomicelles can inhibit the metastasis of breast cancer cells.