Nanomedicine Regulating Tumor Microenvironment For Cancer Treatment

Cancer is the well-deserved"first killer"of human beings,and it is a serious threat to human life and health.However,conventional treatment methods include surgery,radiotherapy,and high-circulating dose chemotherapy.The treatment efficiency is low and far from meeting the needs of cancer treatment.New and efficient treatment methods are urgently needed to be developed.On the one hand,the rapid development of nanotechnology and the emergence of numerous nanomaterials have brought hope for the development of new cancer treatments.When the size of the material reaches the nano-scale,it has completely different properties from the macro-scale material,such as increased active surface sites,enhanced catalytic activity,and more abundant surface functional groups.Some nano-materials also have unique acoustic,electrical,thermal,magnetic,optical and other properties,which can realize the diagnosis and treatment of cancer at the same time.On the other hand,the advancement and development of medicine have given us a more comprehensive and in-depth understanding of cancer,which is the result of the interaction between malignant cells and the surrounding environment.They change and support each other.To cure cancer,we should not simply kill tumor cells,but start with the entire tumor microenvironment,and conduct comprehensive and thorough intervention and treatment to cancer.Taking the tumor microenvironment as a breakthrough,this article designs and synthesizes a variety of new nanomedicines,studies their anti-tumor effects and deeply explores the mechanism of action.The work in this paper is divided into the following aspects:In Chapter 1,we made a brief summary of the research and development status of nanomaterials,and introduced the composition and basic characteristics of the tumor microenvironment.In Chapter 2,we designed and constructed a Pt-based core-shell nano-system based on the hypoxia characteristics of the tumor microenvironment.The excess hydrogen peroxide in the tumor is catalytically converted into oxygen,which relieves the tumor’s hypoxia while improving the effect of photodynamic therapy（PDT）.The design of the core-shell structure is beneficial to separate the generation of oxygen from the conversion of oxygen to ¹O₂,which not only reduces the interference between reactions,but also shortens the diffusion distance of ¹O₂ and reduces the quenching of ¹O₂.When there is no light,the nano system can continuously produce oxygen to relieve tumor hypoxia;when light is applied,the generated oxygen is converted into ¹O₂,which enhances the effect of tumor treatment.The different parts of the nanomaterial perform their duties,avoiding mutual interference of reactions,and providing powerful material support for efficient tumor treatment like an efficient nano-factory.In Chapter 3,we introduce gas therapy into cancer treatment based on the structural characteristics of the tumor microenvironment.We have designed and constructed a nano system that releases CO in response to light,which can kill tumor cells by increasing the CO concentration in the tumor microenvironment.In tumor,deformed blood vessels,chaotic structures,and increased tissue fluid pressure all create barriers for drug delivery.Studies have found that many small gas molecules have a certain regulatory effect on tumors.In addition,gas has the characteristics of good permeability and fast diffusion.We introduce gas therapy into tumor treatment.We have developed a safe and stable CO delivery system that can rapidly increase the CO concentration in the tumor microenvironment under light stimulation,damage the mitochondria of cancer cells,trigger cell autophagy,and ultimately lead to the death of cancer cells.The iron oxide shell layer of the nano system prevents the leakage and oxidation of carbonyl iron,enhances biological safety,and improves the effect of tumor treatment.In Chapter 4,we explored the interaction between nanoparticles and the tumor microenvironment.We synthesized nanoparticles that can slowly disintegrate outside the cell,studied the biological effects of the nanoparticles in cancer cells,and discussed the interaction between the tumor microenvironment and nanomedicine.We found that after the nanoparticles disintegrated,they enter and accumulate in the cell nucleus.At the same time,the disintegrated nanoparticles cause a series of biological effects such as mitochondrial damage and cell autophagy,which ultimately leads to long-term inhibition of tumor cell proliferation.