title: Hydrazinocurcumin Encapsuled nanoparticles "re-educate" tumor-associated macrophages and exhibit anti-tumor effects on breast cancer following STAT3 suppression.
abstract: Tumor-associated macrophages (TAMs) are essential cellular components within tumor microenvironment (TME). TAMs are educated by TME to transform to M2 polarized population, showing a M2-like phenotype, IL-10(high), IL-12(low), TGF-β(high). STAT3 signaling triggers crosstalk between tumor cells and TAMs, and is crucial for the regulation of malignant progression. In our study, legumain-targeting liposomal nanoparticles (NPs) encapsulating HC were employed to suppress STAT3 activity and "re-educate" TAMs, and to investigate the effects of suppression of tumor progression in vivo. The results showed that TAMs treated by HC encapsuled NPs could switch to M1-like phenotype, IL-10(low), IL-12(high), TGF-β(low), and the "re-educated" macrophages (M1-like macrophages) considerably demonstrated opposite effect of M2-like macrophages, especially the induction of 4T1 cells migration and invasion in vitro, and suppression of tumor growth, angiogenesis and metastasis in vivo. These data indicated that inhibition of STAT3 activity of TAMs by HC-NPs was able to reverse their phenotype and could regulate their crosstalk between tumor cells and TAMs in order to suppress tumor progression.
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Zhang
authors.forename: Wenxia
authors.initials: W
authors.lastname: Tian
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Cai
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Weiqi
authors.initials: W
authors.lastname: Dang
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Tingmei
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006834:Hydrazines / Q000737:chemistry / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D006834:Hydrazines; D050796:STAT3 Transcription Factor; C475807:hydrazinocurcumin; D003474:Curcumin