BP-1-102

Nucleic acid drug delivery remains a key challenge in the development of nucleic acid therapy. How to improve the efficiency of nucleic acid delivery is still an important strategy for Lipofectamine 3000 and LNP development. Here, we screened 248 inhibitors or agonists related to immune modulation and identified three small molecules (BP-1-102, SCH58261, and Bropirimine) that could enhance the transfection efficiency to 2-fold to 5-fold of Lipofectamine 3000 and LNP, all of which are currently approved for clinical use in the treatment of the most common malignant tumors. In addition, we used high-throughput RNA sequencing technology to analyze the mechanisms and found that they were mainly associated with the receptor-mediated endocytosis pathway. Our findings have yielded novel insights that can contribute to the advancement of nucleic acid drugs, enhancing both their efficacy and precision in targeting cancer therapy.

Disulfidotosis is a newly identified form of cell death associated with tumor response, patient outcomes, and cancer progression. This study aims to identify disulfidptosis‐related genes (DiRGs) and their role in osteosarcoma (OS) to predict prognosis and optimize drug therapy for better patient survival. Gene expression matrices and clinical information on OS were obtained from the TARGET and GEO databases. Unsupervised clustering analysis identified two DiRG molecular subgroups with significantly different intratumoral heterogeneity and tumor microenvironment cell infiltrating characteristics in OS. A robust disulfidptosis‐related prognostic model using five DiRGs was developed, demonstrating excellent predictive and prognostic power in OS with AUC values of 0.69, 0.78, and 0.85 for 1‐, 3‐, and 5‐year periods, respectively. Investigations into the impact of disulfidoptosis on immune status in OS patients across different risk subgroups revealed that a low immune score and compromised immune status were associated with an unfavorable prognosis for OS patients. INF2 and MEGF10 genes are highly reliable predictors of metastasis among the hub DiRG genes. The validation results indicate a robust correlation between the expression of INF2 and MEGF10 and the severity of malignancy and metastasis in OS. Six drugs targeting osteosarcoma metastasis were identified, with INF2‐BP‐1‐102 and MEGF10‐AS703569 showing the best docking scores, indicating their potential to treat OS metastasis effectively. These findings provide valuable insight into improving treatment for OS patients.