ArticleNanomedicine (London, England)2025
Thermo-responsive nano-hydrogel-based delivery of Saikosaponin a to enhance anti-PD-1 therapy in osteosarcoma.
Article in Nanomedicine (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
6 authors.
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Abstract
objectiveThis study aimed to identify key targets of Saikosaponin A (SSA) in treating osteosarcoma (OS) using network pharmacology and transcriptomics, and to develop a temperature-sensitive hydrogel nanocomplex delivering SSA in combination with the PD-1 inhibitor pembrolizumab to enhance anti-tumor effects.
methodsThrough network pharmacology and transcriptomic analysis, 23 co-regulated genes were identified, leading to the construction of a prognostic risk model containing four core genes. Molecular dynamics simulations were employed to explore the binding interaction between SSA and the key target FASN. The Gel@PLGA@SSA@FA was synthesized and characterized. Its cytotoxicity and therapeutic effects were evaluated in OS cell lines, both alone and in combination with pembrolizumab.
resultsFASN was validated as a poor prognostic marker in OS, and molecular simulations confirmed that SSA can effectively bind to FASN. Gel@PLGA@SSA@FA significantly downregulated FASN and CD279 mRNA expression, especially when combined with pembrolizumab. In vitro release studies demonstrated sustained drug release under tumor-mimicking conditions. Functional assays revealed that the combination treatment markedly suppressed OS cell proliferation and migration, induced apoptosis, and exhibited low toxicity toward normal cells.
conclusionThe combination of Gel@PLGA@SSA@FA with pembrolizumab shows strong synergistic anti-tumor effects, offering a promising and biocompatible strategy for enhanced OS therapy.
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