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Updated: Sep 9, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Dectin-1-targeted pH-responsive liposomal nanoplatform delivering Plantago Asiatica L. acidic polysaccharide for
Wanbing Pan1,2, Can Li3,4, Xiaoyu Zhou3,4
1State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
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:
The construction, physical stability, biocompatibility and targeting capability of PLP-II/MGlu-Curd-Lips were evaluated using 1H 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 that the PLP-II/MGlu-Curd-Lips accumulated at the tumor sites and efficiently promoted DCs activation, tumor-associated macrophages (TAMs) polarization, and cytotoxic T lymphocytes (CTLs) infiltration. Consequently, this remodeling of the tumor microenvironment significantly inhibited the growth of 4T1 breast tumors. Importantly, RNA-Seq confirmed that this therapeutic approach promoted the upregulation of genes related to p53 and NF-κB signaling pathways, thereby enhancing immune activation and tumor-suppression effect.
Conclusions:
This study establishes curdlan-modified liposomes as the dual-functional nanoplatform that synergistically enhances DC-targeted delivery of PLP-II and systemic immune activation, providing a promising strategy to augment cancer immunotherapy.
