ArticleAAPS PharmSciTech2022
Polysialic Acid Self-assembled Nanocomplexes for Neutrophil-Based Immunotherapy to Suppress Lung Metastasis of Breast Cancer.
Article in AAPS PharmSciTech, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 12 citations in OpenAlex.
- Toluidine Blue for the Determination of Binding of Anionic Polysaccharides to Lipid Raft Domains by Absorption Spectroscopy.Membranes · 2025Article
- Neutrophil-targeted liposomal platform: A shift in novel approach for early detection and treatment of cancer metastasis.Asian journal of pharmaceutical sciences · 2024Article
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8 authors at 1 institution in 1 country.
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Abstract
The role of neutrophils in tumor metastasis has recently attracted widespread interest. Neutrophils are the most abundant immune cells in human peripheral blood, and large numbers can spontaneously migrate to metastatic sites, where they form an immunosuppressive microenvironment. Polysialic acid (PSA) can target peripheral blood neutrophils (PBNs) mediated by L-selectin, and abemaciclib (ABE) and mitoxantrone (MIT) can treat immunosuppressive microenvironments. Here, we aimed to inhibit lung metastasis of breast cancer and improve chemoimmunotherapy by designing a PSA-modified ABE and MIT co-delivery system (AM-polyion complex (PIC)) to target PBNs in mice with metastatic tumors. We found that through electrostatic interactions between the strong negative charge of PSA and the positive charge of the drug can form stable nanocomplexes and that spontaneous migration of neutrophils can mediate the aggregation of these complexes in the lungs, induce antimetastatic immune responses, enhance the effectiveness of cytotoxic T lymphocytes (CTLs), and inhibit regulatory T cell (Treg) proliferation in vivo and in vitro. Pharmacodynamic results suggested that neutrophil-mediated AM-PIC chemoimmunotherapy inhibited tumor metastasis in mice with lung metastasis of 4T1 breast cancer. Overall, PSA-modified nanocomplexes offer promising neutrophil-mediated, targeted drug delivery systems to treat lung metastasis of breast cancer.
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