Poly(ferulic acid)nanocarrier enhances chemotherapy sensitivity of acute myeloid leukemia by selectively targeting inflammatory macrophages  

作　　者：Weijian Zhang Xianyu Deng Liying Wang Jian Wang Xiuting Guo Lianggui Huang Xinyi Wang Jun Wu Linjia Jiang 

机构地区：[1]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China [2]Department of Otolaryngology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China [3]Department of Hematology,The Seventh Affiliated Hospital,Sun Yat-sen University,Shenzhen 518107,China [4]Department of Pediatrics,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China [5]Bioscience and Biomedical Engineering Thrust,The Hong Kong University of Science and Technology(Guangzhou),Nansha,Guangzhou 511400,China [6]Division of Life Science,The Hong Kong University of Science and Technology,Hong Kong SAR 999077,China

出　　处：《Chinese Chemical Letters》2024年第9期289-295,共7页中国化学快报（英文版）

基　　金：the National Key Research and Development Program of China(No.2022YFA1103302);the National Natural Science Foundation of China(Nos.92268205,52173150,51973243,82204287);Guangdong Innovative and Entrepreneurial Research Team Program(No.2019ZT08Y485);Guangdong Basic and Applied Basic Research Foundation(No.2021B1515020012);Guangzhou Science and Technology Program City-University Joint Funding Project(No.2023A03J0001).

摘　　要：Macrophages,as a subset of innate immune cells,play a pivotal role in the initiation,maintenance,and resolution of inflammatory responses during tissue damage repair,defense against infections,and tumor progression.However,the mechanisms by which macrophages regulate inflammation in acute myeloid leukemia(AML)and their involvement in the chemotherapeutic effect remain elusive.In this study,we have identified that AML cells stimulate macrophage expansion by activating the colony-stimulating factor 1 receptor(CSF1R)pathway.The expanded macrophages activate nuclear factor kappa-B(NFκB)to induce the expression of inflammatory factors,thereby maintaining leukemic cell quiescence and promoting cell survival following chemotherapy.Furthermore,we have successfully utilized a poly(ferulic acid)nanocarrier to selectively target macrophages for inhibiting the NFκB-mediated inflammation,ultimately enhancing chemotherapy efficacy against AML.Taken together,our findings highlight the crucial role of macrophage-induced inflammation in conferring chemoresistance to AML,and demonstrate the potential of a targeted nanocarrier specifically designed for inflammatory macrophages to improve the AML chemotherapeutic outcomes.

关 键 词：Acute myeloid leukemia CHEMORESISTANCE MACROPHAGE Inflammation NFΚB 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R733.71[医药卫生—肿瘤]