Nanomedicine Regulates Oxidative Stress To Intervene Chronic Diseases

Recently years,the treatment of diseases tends to develop from single therapy to combined therapy.Compared with single therapy,combined therapy has outstanding advantages in treatment efficiency.Inflammatory and cell proliferation are closely related to cellular oxidative stress level.It is more important to improve therapeutic efficiency through synergistic effect than single therapy for anti-inflammatory and proliferative.It is limited to the combined application of small molecule,nucleic acid or protein,due to the problems of poor stability and easy to miss the target.A new therapeutic model for drug collaborative therapy has been provided,while the rapid development of nanoscience and technology,as well as the design and development of multifunctional composite nanocarriers.This paper focuses on how to solve the problems of poor targeting and instability of drugs through the assistance of nanocarriers.Starting from the design and synthesis of three types of novel composite nanomaterials,and studies on the anti-inflammation,anti-oxidation and promoting cardiomyocyte proliferation.The main research contents are as follows:1.Reducing the inflammatory response is a major goal in the therapy of rheumatoid arthritis（RA）.Herein,we integrated palladium nanoparticles（Pd NPs）with selenium nanoparticles（Se NPs）and obtained a multiple nanosystem（Pd@Se-HA NPs）that could simultaneously scavenge hydroxyl radicals（·OH）and provide a photothermal effect.The Pd@Se-HA NPs were constructed by a simple selfassembly method in which Se NPs were electrostatically bonded to Pd NPs;hyaluronic acid（HA）was linked to the NPs by ester bonding to provide macrophage targeting ability.The experiments show that the combined therapy of eliminating·OH with Se NPs and utilizing PTT with Pd NPs could effectively reduce the inflammatory response in macrophages more effectively than either individual NP treatment.In addition,the outer layer of HA could specifically target the CD44receptor to enhance the accumulation of Pd@Se NPs at the lesion,further enhancing the therapeutic effect.After treatment for 15 days,the Pd@Se-HA NPs nearly eliminated the inflammatory response in the joints of mice in an induced RA model,and prevented joint damage and degradation.2.Myocardial cell mitochondria-targeted mesoporous polydopamine nanoparticles eliminate inflammatory damage in cardiovascular disease.Excess ROS produced by inflammatory damage is a direct factor in myocardial injury death.And anti-oxidant therapy is an effective measure to prevent rapid death of cardiomyocyte cell.Cysteine is a potent antioxidant and antidote,and it is instability because of the instability.It is important to protect the sulfhydryl and improve its stability.Mitochondria are the main sites of ROS production.Therefore,the targeted and stable delivery of cysteine to mitochondria for regulating mitochondrial function is an effective strategy to efficiently eliminate ROS and prevent inflammatory damage.In this paper,we developed a targeting drug delivery nano-platform of Mesoporous polydopamine by loading cysteine and coupling mitochondria-targeted triphenylphosphine with nanoparticles（Cys-MPDA@TPP NPs）,that could double-collaborative treatment with targeted delivery and antioxidant,and enhanced ROS elimination efficiency.3.Double si RNA Nanomedicine Stabilized delivery by mesoporous nano-selenium for Inhibition of ROX and Cardiac Proliferation.In this chapter,we synthesized and compared a gene delivery system(Se NPs-si RNA^Meis1&Hoxb13)on cardiomyocyte proliferation.Mesoporous nano-selenium with good antioxidant carrier was selected to deliver double small interfering RNAs(si RNA^Meis1 and si RNA^Hoxb13)by electrostatic action.The internalized nanomaterials reduce ROX levels and the toxicity of drugs on cells,and reduce intracellular oxidative stress,then extending the proliferation of cardiomyocytes.Se NPs-si RNA^Meis1&Hoxb13 gene delivery system inhibited the expression of Meis1 and Hoxb13 genes in cardiomyocytes,by double Interactions for the division and proliferation of adult cardiomyocytes.Based on the design and synthesis of nanomaterials,we have constructed three new types of composite nanomaterials and proposed three new strategies for diseases therapy,such as inhibition of the macrophage inflammatory response in rheumatoid arthritis,regulation of myocardial cell mitochondrial function to prevent cardiovascular inflammatory damage,and inhibition of ROX and promotion of cardiomyocyte proliferation.The research in this paper provides a new paradigm for the efficient treatment of antioxidant,anti-inflammatory and related diseases.