A Cascade-Amplified Pyroptosis Inducer: Optimizing Oxidative Stress Microenvironment by Self-Supplying Reactive Nitrogen Species Enables Potent Cancer Immunotherapy.

التفاصيل البيبلوغرافية
العنوان:	A Cascade-Amplified Pyroptosis Inducer: Optimizing Oxidative Stress Microenvironment by Self-Supplying Reactive Nitrogen Species Enables Potent Cancer Immunotherapy.
المؤلفون:	Ye B; Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou, Zhejiang 310009, China.; The Second Affiliated Hospital of Zhejiang University Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009, China.; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310009, China., Hu W; Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China., Yu G; Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China., Yang H; MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China., Gao B; Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou, Zhejiang 310009, China.; The Second Affiliated Hospital of Zhejiang University Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009, China.; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310009, China., Ji J; MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China., Mao Z; Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China., Huang F; Stoddart Institute of Molecular Science, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310027, China.; Zhejiang-Israel Joint Laboratory of Self-Assembling Functional Materials, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang 311215, China., Wang W; Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou, Zhejiang 310009, China.; The Second Affiliated Hospital of Zhejiang University Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009, China.; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310009, China., Ding Y; Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, China.; Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou, Zhejiang 310009, China.; The Second Affiliated Hospital of Zhejiang University Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009, China.; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310009, China.
المصدر:	ACS nano [ACS Nano] 2024 Jul 02; Vol. 18 (26), pp. 16967-16981. Date of Electronic Publication: 2024 Jun 18.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: American Chemical Society Country of Publication: United States NLM ID: 101313589 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1936-086X (Electronic) Linking ISSN: 19360851 NLM ISO Abbreviation: ACS Nano Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Washington D.C. : American Chemical Society
مواضيع طبية MeSH:	Pyroptosis/drug effects , Reactive Nitrogen Species/metabolism , Immunotherapy* , Oxidative Stress/drug effects , Tumor Microenvironment/drug effects, Animals ; Mice ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism ; Humans ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Melanoma, Experimental/therapy ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology
مستخلص:	Selective generation of sufficient pyroptosis inducers at the tumor site without external stimulation holds immense significance for a longer duration of immunotherapy. Here, we report a cascade-amplified pyroptosis inducer CSC CPT/SNAP that utilizes reactive nitrogen species (RNS), self-supplied from the diffusion-controlled reaction between reactive oxygen species (ROS) and nitric oxide (NO) to potentiate pyroptosis and immunotherapy, while both endogenous mitochondrial ROS stimulated by released camptothecin and released NO initiate pyroptosis. Mechanistically, cascade amplification of the antitumor immune response is prompted by the cooperation of ROS and NO and enhanced by RNS with a long lifetime, which could be used as a pyroptosis trigger to effectively compensate for the inherent drawbacks of ROS, resulting in long-lasting pyroptosis for favoring immunotherapy. Tumor growth is efficiently inhibited in mouse melanoma tumors through the facilitation of reactive oxygen/nitrogen species (RONS)-NO synergy. In summary, our therapeutic approach utilizes supramolecular engineering and nanotechnology to integrate ROS producers and NO donors of tumor-specific stimulus responses into a system that guarantees synchronous generation of these two reactive species to elicit pyroptosis-evoked immune response, while using self-supplied RNS as a pyroptosis amplifier. RONS-NO synergy achieves enhanced and sustained pyroptosis and antitumor immune responses for robust cancer immunotherapy.
فهرسة مساهمة:	Keywords: immunotherapy; nitric oxide; pyroptosis; reactive oxygen/nitrogen species; supramolecular prodrug nanoassemblies
المشرفين على المادة:	0 (Reactive Nitrogen Species) 0 (Reactive Oxygen Species) 0 (Antineoplastic Agents)
تواريخ الأحداث:	Date Created: 20240618 Date Completed: 20240702 Latest Revision: 20240702
رمز التحديث:	20240702
DOI:	10.1021/acsnano.4c03172
PMID:	38888082
قاعدة البيانات:	MEDLINE

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الوصف
تدمد:	1936-086X
DOI:	10.1021/acsnano.4c03172