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Advanced materials: colorectal tumor microenvironment activates catabolism Cu2O@CaCO3 Synergetic tumor therapy based on traditional Chinese Medicine

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Colorectal cancer is a common malignant tumor of the digestive tract. Its incidence rate mortality rate are high. It is the fourth leading cause of death related to cancer. Kdsps The growth of colorectal cancer is relatively slow the early detection rate is not high metastasis is easy to occur so many patients lose the opportunity of effective treatment. Lin Jun a research team of Changchun Institute of Applied Chemistry Chinese Academy of Sciences Hou Zhiyao a team of Professor of Guangzhou Medical University have developed an anti-tumor synergistic treatment system activated by colorectal tumor microenvironment which integrates precise treatment of primary lesions systemic treatment of metastatic lesions.

at present surgery combined with preoperative or postoperative adjuvant chemoradiotherapy is the stard clinical means of colorectal cancer treatment. Surgical resection is the first choice of treatment in clinic. However for the treatment of low rectal cancer it is extremely difficult to maintain the integrity of anal function. In addition for patients with advanced cancer with distant metastasis surgical resection is ineffective. For patients with cancer metastasis radiotherapy chemotherapy is the main treatment but its side effects such as bone marrow suppression intestinal obstruction cardiotoxicity other complications seriously affect the therapeutic effect. In recent years although immune checkpoint therapy has been approved by regulatory authorities for the treatment of tumors with severe mutations microsatellite instability only a small number of patients can achieve significant therapeutic effects.

with the development of nanotechnology anticancer nanodrugs have become a hot research field of interdisciplinary researchers. In order to improve the treatment efficiency it has shown great application prospects to integrate a variety of treatment modes into a nano drug for collaborative treatment. However due to the lack of specificity of tumor location the existing single or combined treatment methods have some disadvantages or limitations which make the treatment of colorectal cancer unable to achieve the expected results. The design of a tumor microenvironment activated nanocomposite provides an efficient responsive treatment mode for precise targeted cancer treatment. It can not only achieve synchronous effective inhibition of primary metastatic lesions but also reduce tumor metastasis recurrence reduce toxic side effects. Colorectal cancer patients in different stages can obtain targeted treatment. Professor Lin Zhijun's team of "spkds" "spkds" Cu2O@CaCO3 Nanodrugs can be metabolized to achieve activated synergistic therapy. Cu2 XS with photothermal conversion photocatalysis Fenton like reaction can be obtained by the reaction of Cu2O nanoparticles with H2S. The acidic decomposition of CaCO3 as a protective shell can prevent Cu2O from being sulfonated by endogenous H2S in normal tissues before reaching colorectal tumor lesions. Cu2O@CaCO3 When it reaches the colorectal tumor the protective shell of CaCO3 decomposes releases calcium ions in the acidic tumor microenvironment leading to Ca2 overload in cancer cells. Subsequently the hollow porous Cu2O which lost its protection in the tumor microenvironment reacted rapidly with endogenous H2S to form ultra-small cu31s16 nanodrug. Cu31s16 which has strong absorption in the whole near-infrared region can achieve the photothermal therapy excited by 1064 nm near-infrared light (supplemented by photodynamic / chemokinetic / calcium overload therapy in the system) has a good removal effect on colorectal tumors in situ. After treatment the ultra-small cu31s16 can be metabolized to the body through urine through renal filtration system effectively avoiding the harm caused by long-term retention of inorganic nanoparticles in the body. Furthermore combined with CD47 checkpoint blockade by reprogramming M2 tumor associated macrophages that promote tumor growth to M1 macrophages that kill tumor the tumor microenvironment of immunosuppression can be effectively reversed thus initiating the immune response regulated by T cells which can effectively inhibit the growth of invasive tumor distal secondary tumor. Therefore the tumor microenvironment of colorectal cancer is activated Cu2O@CaCO3 It can achieve accurate efficient "stimulus response" treatment of colorectal cancer. The research results were published on doadmi (1004610.0020247).

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