Dectin-1-targeted pH-responsive liposomal nanoplatform delivering Plantago Asiatica L. acidic polysaccharide for immunomodulation and immunosuppressive breast cancer microenvironment reprogramming

作者：Wanbing Pan, Can Li, Xiaoyu Zhou, Wei Liu, Jintong Liu, Qiao Lin, Jinglin Huang, Zhihui Hao, Yanyan Jiang, Jiahao Lin · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03638-x · 被引用次数：8 · 研究领域：Nanoplatforms for cancer theranostics、Nanoparticle-Based Drug Delivery、Immune cells in cancer

BACKGROUND: The limited tumor-specific delivery and insufficient dendritic cell (DC) activation remain critical challenges in cancer immunotherapy. This research aimed to improve antitumor efficacy by developing a novel pH-responsive liposomal nanoplatform that specifically targets DC via Dectin-1 recognition in the tumor microenvironment (TME), thereby enhancing cellular immunity, minimizing off-target toxicity and reprograming the tumor immunosuppressive TME. METHODS: H NMR spectra, FT-IR spectroscopy, TEM, LUMiSizer assay, CCK-8 assay, Flow Cytometry (FC), and IVIS imaging. Therapeutic efficacy was assessed through FC, H&E staining, TUNEL, and immunohistochemical staining. The antitumor mechanism of action of PLP-II/MGlu-Curd-Lips in murine 4T1 breast tumors was investigated using RNA sequencing. RESULTS: A Dectin-1-targeted pH-responsive liposomal nanoplatform (PLP-II/MGlu-Curd-Lips) was developed for spatiotemporally controlled delivery of Plantago asiatica L. acidic polysaccharide (PLP-II). The nanocarrier featured a curdlan-grafted copolymer backbone with pH-cleavable 3-methyl glutarylated moieties and demonstrated an ideal particle size and enhanced stability, enabling tumor acidity-triggered payload release, Dectin-1-mediated DC targeting, and enhanced cytoplasmic delivery via lysosomal escape. The prepared nanocarriers exhibited obvious lysosomal accumulation, and they significantly improved the co-stimulation and migration ability of DCs. In vivo studies indicated ...