Design And Assembly Of Nanodrug System For Synergistic Cancer Therapy

As a kind of malignant diseases,cancer has been a major public health problem in the world.Traditional cancer treatments,including chemotherapy,radiotherapy and surgical treatment,have some limitations and poor treatment effects.Therefore,it is urgent to develop an effective and safe cancer multimodal therapy.Owing to minimal invasiveness,negligible drug resistance,and high therapeutic selectivity,photodynamic therapy has emerged as a powerful technique for cancer treatment.With clear and easily modifiable structure,mussel-inspired dopamine-based nanomaterials have been widely investigated for biomedical applications.In this thesis,by using the small molecule dopamine as the building block,we synthesized two responsive nanodrug delivery systems combining chemotherapy and photodynamic therapy.The main research results are summarized as follows:?1?Novel dopamine-based nanoparticles with excellent biocompatibility and water solubility were prepared via one-step covalent assembly of dopamine and genipin.The size of the nanoparticles could be conveniently controlled by changing the concentration and the ratio of two building blocks.These dopamine-based nanoparticles could not only play as the intrinsic photosensitizer for photodynamic therapy,but also act as nanocarriers to load anticancer drug bortezomib?Btz?via catechol-boronate linkage.The complex nanoparticles converted O₂ to singlet oxygen?¹O₂?under a 635 nm laser irradiation,and the pH-responsive boronate esters were broken in the acid tumor microenvironment facilitating the drug release.Therefore,as-designed DGNPs-Btz complex induced apoptosis of HeLa cells in vitro with combined photodynamic therapy and chemotherapy.The DGNPs-Btz complex finally showed enhanced anticancer efficacy compared with individual therapy.?2?The dopamine-based nanoparticles were successfully prepared via covalent self-assembly of dopamine and glutaraldehyde.The nanoparticles showed pH-responsiveness and autofluorescence properties due to the dynamic Schiff base bond.Furthermore,the anticancer drug DOX and photosensitizer Ce6 were adaptively encapsulated into the nanocarriers to construct a drug delivery system integrating chemotherapy and photodynamic therapy.The complex drug delivery system could responsively release the encapsulated drugs in the acid tumor microenvironment and produce abundant oxygen species under a 660 nm laser irradation.As a result,the synergistic system of photodynamic therapy and chemotherapy induced apoptosis of HeLa cells in vitro and showed significant anticancer efficacy.