Tumor-Associated Macrophages Regulating a Polymer Nanoplatform for Synergistic Treatment of Breast Tumors

• DOI: 10.1021/acsami.3c05497
• Publication Date: 2023-07-18T11:01:23Z
• Authors: Li Zhang; Shuai Cui; Ning Ding; Jing Zhang; Enna Cui; Qian Xiang; Zhenghao Zhou; Bo Sun; Yinan Wang; Hao Hong; Yunsu Ma; Dongzhi Yang
• Keywords: CD86; Tumor progression

Tumor-associated macrophages (TAMs) play a critical role in tumor progression and metastasis. Modulation of TAM polarization is one the most effective strategies to change immunosuppressive microenvironment (TME). In this study, organic polymer nanoparticles (CPHT) were prepared using hyaluronic acid (HA)-conjugated disulfide-bonded polyethylene imide (PEIS) as carrier through self-assembly strategy. These modified by transferrin (Tf) loaded with chlorin e6 (Ce6). The results showed that CPHT had good dispersion particle size about 30 nm. gradually disintegrated under exposure high concentration glutathione (GSH) cells, proving possibility for controlled release Ce6 photodynamic therapy. An vitro test uptake cells was mediated both HA Tf, indicating active tumor-targeting capacity CPHT. significantly downregulated ratio CD206/CD86 triggered upregulation immune factors such TNF-α iNOS, suggesting repolarization TAMs. We also found effectively induced ferroptosis lipid peroxide accumulation, GSH depletion, downregulation peroxidase (GPX4) expression. Animal experiments confirmed not only inhibited growth tumors situ but decelerated distal tumor. Elevated levels CD86 IFN-γ decreased expression CD206 observed at sites post treatment. value multifunctional nanoplatform can tune TME provide new hope