Utrasmall Cu_2-xSe Nanoprobe For Breast Cancer And Glioma Therapy

A new path opened for cancer therapy with the development of nanotechnology.Nanomaterials,with the versatile chemical propertie and convenient process of surface modification,own natural advantage in cancer treatmen.Especially,there are some specific functional namomaterials can response both to exogenous stimuli(such as ultrasound,X-ray,magnetic and heat,etc.)and tumor microenviroment(such as H2O2,pH and GSH,etc.).Guiding by the need of clinical,the multi-fnctional Cu2-xSe nanoprobe with good biocompatibility could be synthesized through the technology of chemical synthesis.Aim to investigate the Cu2-xSe nanoprobe used for cancer could response to both exogenous stimuli and tumor microenviroment.The bottleneck of the cancer therapy by reactive oxide species(ROS)can be soved by the basic research of medical nanomaterials.The main research topics are present show as below:Chapter 1:A brief overiew of ROS and cancer therapy.Firstly,the basis theoretical of cancer therapy by ROS is introduced.Secondly,the main methods for the treatment of tumors with ROS are summarized.Therefore,the research on the biomimetic nanomaterials construction technology to improve the functionality of nanomaterials is detailly introduced.And then,the tumor immunotherapy mediated by ROS is elaborated.Finally,the basis and research contents of the topic are clarified.Chapter 2:Relief hypoxic microenvironment in tumor to improve photodynamic treatment for breast cancer.An ultrasmall O2-evolving nanoplatform(3.1 ± 0.4 nm in size),which was fabricated from polyethylene glycol modified(PEGylated)Cu2-xSe nanoparticles,β-cyclodextrin,and chlorin e6 under ambient conditions.The excellent PDT performance of this nanoprobe is owing to the unique properties of ultrasmall Cu2-xSe nanoprobe actted as a Fenton-like catalyst for the degradation of H2O2 to release O2 for reaction with chlorin e6 to form singlet oxygen(1O2)under the same irradiation.Significantlly,improve the production of ROS,which could massively destroy tumor cells and lead to excellent therapeutic efficacy improving the PDT.Chapter 3:Boosting H2O2-guided chemodynamic therapy of breast cancer by enhancing reaction kinetics through versatile biomimetic fenton nanocatalysts and the second near-infrared light irradiation.Biomimetic nanocatalysts are composed of ultra-small Cu2-xSe nanoprobe,glucose oxidase,and tumor cell membrane.The nanocatalysts can be retained in tumor for more than 2 days to oxidize glucose and produce about a 2.6-fold increase in H2O2 to enhance Fenton-reaction under the NIR II irradiation just at the maximum H2O2 concentration.This work first demonstrates the CDT treatment of cancer enhanced by the NIR II light guided by H2O2 concentration in tumor.Chapter 4:Anti-tumor immune response of glioma actived by ROS.Biomimetic nanoprobe of Cu2-xSe can be effectively and locally transported into orthotopic brain tumor with the assistance of focused ultrasound.ROS generated by Fenton-like reaction can induce immugenic cell death(ICD)of cancer cell to release antigens which are typically captured by antigen presentation cells(APCs).The APCs can active immature T cells in lymph nodes.The active T cells can move into tumor microenviroment(TME)and target tumor cells to eliminate tumor cells through inducing apoptosis.In addition,ROS play a vital role in macrophage polarization and active,which can facilitate tumor associated macrophages(TAMs)repolarzition toward to M1 type to enhance the antitumor immunity.