Bufalin (buf) has poor solubility in aqueous solution, poor tumor targeting, and many non-specific toxic and side effects. The advantages of high-molecular-weight polymer conjugates are that they can improve the water solubility of buf, prolong plasma half-life, and reduce non-specific toxicity. A novel water-soluble polymer–drug conjugate with buf and fluorescein pendants was prepared by the combination of reversible addition-fragmentation transfer (RAFT) polymerization and click chemistry. Its anticancer performance and cellular uptake behavior against liver cancer were investigated in vitro. The polymer–buf conjugates exhibit controlled release and tumor-targeting capabilities, showing promise for clinical applications.
Background. The aim of this study is to explore the interactions between effective monomers of herbal formulas and their therapeutic targets using systems biology approaches which may be a promising approach to unraveling their underlying mechanisms. Shentao Ruangan decoction (STRGD), which has been experimentally, clinically demonstrated to be effective in treating liver hepatocellular carcinoma (LIHC), was selected. Methods. Bioactive ingredients and drug targets of STRGD were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform and BATMAN-TCM databases. LIHC-related differentially expressed genes (DEGs) and key modules were identified by a weighted gene coexpression network analysis using The Cancer Genome Atlas data. The Kaplan–Meier analysis was used to investigate the relationship between STRGD tumor targets and patients survival. The CIBERSORT deconvolution algorithm was used to analyze the correlation between STRGD tumor targets and infiltrating immune cells. Enrichment analysis was used to analyze biological functions. Interactions between STRGD compounds and LIHC-immune-related genes were investigated using molecular docking and MDS. Results. We identified 24 STRGD tumor targets, which were found to be correlated with survival and the level of immune cell infiltration in LIHC patients. Immune infiltration, gene set enrichment, and Kyoto Encyclopedia of Genes and Genomes analyses highlighted the roles of T and B cell subsets, which were both related to activator protein 1 (AP1), in STRGD action. Docking studies and HPLC indicated that tanshinone IIA is the main compound of STRGD in LIHC treatment, and MDS showed that the potential LIHC-immune-related targets 1FOS and 1JUN firmly bind to tanshinone IIA. Conclusions. The mechanisms of STRGD in improving the immune and survival status of LIHC patients include interactions between STRGD compounds and LIHC-immune-related targets. The findings of this study can guide research studies on the potential usefulness of tanshinone IIA in the development of drugs targeting 1JUN and 1FOS for the treatment of LIHC.
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