Dual-targeting of tumor cells and subcellular endoplasmic reticulum via AgPPIX-based Janus nanoparticles for photodynamic/immunotherapy against TNBC.

Autor: Ma K; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Diao H; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Xu X; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Jin Y; Department of Histology and Embryology, Dalian Medical University, Dalian 116044, Liaoning Province, China. mahaiying@dmu.edu.cn., Qiu M; Department of Histology and Embryology, Dalian Medical University, Dalian 116044, Liaoning Province, China. mahaiying@dmu.edu.cn., Liu Z; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Yang C; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Zhao J; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Chai S; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Fang Q; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Guo Z; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Cui C; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn., Xu J; School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, China. makunonline@dlut.edu.cn.; Panjin Institute of Industrial Technology, Dalian University of Technology, Panjin 124221, China., Yin L; Department of Oncology, Central Hospital of Dalian University of Technology, Dalian 116033, China. lwyin_2018@163.com., Ma HY; Department of Histology and Embryology, Dalian Medical University, Dalian 116044, Liaoning Province, China. mahaiying@dmu.edu.cn.
Jazyk: angličtina
Zdroj: Nanoscale [Nanoscale] 2024 Jun 27; Vol. 16 (25), pp. 12095-12106. Date of Electronic Publication: 2024 Jun 27.
DOI: 10.1039/d4nr01139b
Abstrakt: Triple-negative breast cancer (TNBC) is known for its strong invasiveness, high recurrence rates, and poor prognosis. Heme oxygenase-1 (HO-1) is closely related to tumor invasion, metastasis, recurrence and formation of tumor immunosuppression. The expression of HO-1 is high in TNBC and low in normal tissues. In this study, AgPPIX was synthesized as a heme oxygenase-1 (HO-1) inhibitor and a photosensitizer for TNBC therapy. PDA nanoparticles were synthesized and modified with anti-CD24 and p -toluenesulfonamide (PTSC) on their both sides to obtain PTSC@AgPPIX/PDA@anti-CD24 Janus nanoparticles (PAPC) for AgPPIX-targeted delivery. Anti-CD24 is targeted to CD24 on tumor cells and the PTSC moiety is targeted to endoplasmic reticulum (ER), where HO-1 is located. The results indicated that PAPC Janus nanoparticles exhibited higher cytotoxicity in 4T1 cells than that of the mono-modified nanoparticles. PAPC not only inhibited the expression of HO-1 and VEGF but also reduced TrxR activity significantly. Furthermore, PAPC not only promoted intracellular ROS production under laser irradiation for tumor photodynamic therapy (PDT) but also polarized TAMs from M2-type to M1 for tumor immunotherapy. In vivo experiments confirmed that PAPC could remodel the tumor immune microenvironment and almost completely inhibit the tumor growth in mouse models. Therefore, PAPC Janus nanoparticles are a promising nanoplatform with a dual-targeting capacity for TNBC immune/PDT synergistic therapy.
Databáze: MEDLINE