Citation: Weijian Zhang, Xianyu Deng, Liying Wang, Jian Wang, Xiuting Guo, Lianggui Huang, Xinyi Wang, Jun Wu, Linjia Jiang. Poly(ferulic acid) nanocarrier enhances chemotherapy sensitivity of acute myeloid leukemia by selectively targeting inflammatory macrophages[J]. Chinese Chemical Letters, ;2024, 35(9): 109422. doi: 10.1016/j.cclet.2023.109422 shu

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

Weijian Zhang ^{a, b, 1} ,
Xianyu Deng ^{a, 1} ,
Liying Wang ^{c, 1} ,
Jian Wang ^d ,
Xiuting Guo ^a ,
Lianggui Huang ^a ,
Xinyi Wang ^a ,
Jun Wu ^{e, f, *,} ,
Linjia Jiang ^{a, *,}

a.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
b.
Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
c.
Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
d.
Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
e.
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou 511400, China
f.
Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR 999077, China

junwuhkust@ust.hk

jianglj@mail.sysu.edu.cn

Received Date: 21 October 2023
Revised Date: 3 December 2023
Accepted Date: 10 December 2023
Available Online: 20 December 2023

Figures(4)

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.
- Acute myeloid leukemia,
- Chemoresistance,
- Macrophage,
- Inflammation,
- NFκB
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