دورية أكاديمية
Biomineralization-Tuned Nanounits Reprogram the Signal Transducer and Activator of Transcription 3 Signaling for Ferroptosis-Immunotherapy in Cancer Stem Cells.
| العنوان: | Biomineralization-Tuned Nanounits Reprogram the Signal Transducer and Activator of Transcription 3 Signaling for Ferroptosis-Immunotherapy in Cancer Stem Cells. |
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| المؤلفون: | Zhao Y; Center for Tissue Engineering and Stem Cell Research, Key Laboratory for Autoimmune Disease Research, Department of Hepatic-Biliary-Pancreatic Surgery Affiliate Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang 550025, P. R. China.; School of Life Science, Chongqing University, Chongqing 400044, P. R. China., Fei Y; School of Life Science, Chongqing University, Chongqing 400044, P. R. China., Zhao Y; Division of Nanomaterials and Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, CAS Center for Excellence in Nanoscience, Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Chemistry, Hefei Science Center of CAS, University of Science and Technology of China, Hefei 230026, P. R. China., Li M; School of Life Science, Chongqing University, Chongqing 400044, P. R. China., Hu Y; Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing University, Chongqing 400044, P. R. China., Cai K; Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing University, Chongqing 400044, P. R. China., Yu SH; Division of Nanomaterials and Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, CAS Center for Excellence in Nanoscience, Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Chemistry, Hefei Science Center of CAS, University of Science and Technology of China, Hefei 230026, P. R. China., Luo Z; School of Life Science, Chongqing University, Chongqing 400044, P. R. China. |
| المصدر: | ACS nano [ACS Nano] 2024 Aug 13; Vol. 18 (32), pp. 21268-21287. Date of Electronic Publication: 2024 Jul 31. |
| 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: | Ferroptosis*/drug effects , Neoplastic Stem Cells*/metabolism , Neoplastic Stem Cells*/drug effects , Neoplastic Stem Cells*/pathology , STAT3 Transcription Factor*/metabolism , Immunotherapy* , Signal Transduction*/drug effects, Humans ; Animals ; Mice ; Calcium Phosphates/chemistry ; Calcium Phosphates/pharmacology ; Nanoparticles/chemistry ; Niclosamide/pharmacology ; Niclosamide/chemistry ; Mice, Inbred C57BL ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Cell Line, Tumor ; Hyaluronic Acid/chemistry |
| مستخلص: | Cancer stem cells (CSCs) are promising targets for improving anticancer treatment outcomes while eliminating recurrence, but their treatment remains a major challenge. Here, we report a nanointegrative strategy to realize CSC-targeted ferroptosis-immunotherapy through spatiotemporally controlled reprogramming of STAT3-regulated signaling circuits. Specifically, STAT3 inhibitor niclosamide (Ni) and an experimental ferroptosis drug (1 S , 3 R )-RSL3 (RSL3) are integrated into hyaluronic acid-modified amorphous calcium phosphate (ACP) nanounits through biomineralization (CaP-PEG-HA@Ni/RSL3), which could be recognized by CD44-overexpressing CSCs and released in a synchronized manner. Ni inhibits the CSC-intrinsic STAT3-PD-L1 axis to stimulate adaptive immunity and enhance interferon gamma (IFNγ) secretion by CD8 + T cells to downregulate SLC7A11 and SLC3A2 for blocking glutathione biosynthesis. Meanwhile, Ni-dependent STAT3 inhibition also upregulates ACSL4 through downstream signaling and IFNγ feedback. These effects cooperate with RSL3-mediated GPX4 deactivation to induce pronounced ferroptosis. Furthermore, CaP-PEG-HA@Ni/RSL3 also impairs the immunosuppressive M2-like tumor-associated macrophages, while Ca 2+ ions released from degraded ACP could chelate with lipid peroxides in ferroptotic CSCs to avoid CD8 + T-cell inhibition, thus boosting the effector function of activated CD8 + T cells. This study offers a cooperative ferroptosis-immunotherapeutic approach for the treatment of refractory cancer. |
| فهرسة مساهمة: | Keywords: STAT3; biomineralized nanoassemblies; cancer stem cell treatment; ferroptosis; immunotherapy |
| المشرفين على المادة: | 0 (STAT3 Transcription Factor) 0 (Calcium Phosphates) 0 (STAT3 protein, human) 8KK8CQ2K8G (Niclosamide) 0 (Antineoplastic Agents) 97Z1WI3NDX (calcium phosphate) 9004-61-9 (Hyaluronic Acid) |
| تواريخ الأحداث: | Date Created: 20240731 Date Completed: 20240813 Latest Revision: 20240925 |
| رمز التحديث: | 20240925 |
| DOI: | 10.1021/acsnano.4c05084 |
| PMID: | 39083438 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1936-086X |
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| DOI: | 10.1021/acsnano.4c05084 |