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Abstract Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.

Background: Colorectal cancer (CRC) is a type of malignant gastroenteric tumors associated with a high mortality rate worldwide. Calycosin, a natural phytoestrogen, possesses potent anti-cancer properties. We structurally modified calycosin to improve its physicochemical properties, and generated a novel small molecule termed CA028. Methods: By using network pharmacology, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis and molecular docking, we aimed to predict and disclose the biological functions and mechanism of CA028 in the treatment of CRC through bioinformatic analyses. Results: By searching the online Swiss Target Prediction and TargetNet databases, we identified 150 genes shared by CA028 and CRC. Using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software, we identified 14 hub-functional genes, namely the FYN proto-oncogene, a Src family tyrosine kinase (FYN), mitogen-activated protein kinase 1 (MAPK1), MAPK8, MAPK14, Rac family small GTPase 1 (RAC1), epidermal growth factor receptor (EGFR), protein tyrosine kinase 2 (PTK2), sphingosine-1-phosphate receptor 1 (S1PR1), S1PR2, Janus kinase 1 (JAK1), JAK2, the RELA proto-oncogene NF-κB subunit (RELA), bradykinin receptor B1 (BDKRB1), and BDKRB2. Additionally, biological docking analysis using the Autodock Vina software revealed that FYN and MAPK1 were the main pharmacological proteins of CA028 against CRC. The gene ontology analysis using R-language packages further revealed the anti-CRC functions of CA028, including biological processes, cell components, and molecular pathways. Conclusion: CA028 exhibits effective pharmacological activity against CRC by suppressing the proliferation of CRC cells and improving the tumor microenvironment. Importantly, certain predicted genes (e.g., FYN and MAPK1) may be the pharmacological targets of CA028 in the treatment of CRC.

Owing to the ongoing coronavirus disease 2019 (COVID-19) pandemic, we need to pay a particular focus on the impact of coronavirus infection on breast cancer patients. Approximately 70% of breast cancer patients express estrogen receptor (ER), and intervention therapy for ER has been the primary treatment strategy to prevent the development and metastasis of breast cancer. Recent studies have suggested that selective estrogen receptor modulators (SERMs) are a potential therapeutic strategy for COVID-19. With its anti-ER and anti-viral combined functions, SERMs may be an effective treatment for COVID-19 in patients with breast cancer. In this review, we explore the latent effect of SERMs, especially tamoxifen, and the mechanism between ER and virus susceptibility.