Abstract
Owing to its high degree of malignancy and poor survival outcomes, triple-negative breast cancer (TNBC) is considered the most invasive subtype of breast cancer. In the realm of TNBC treatment, clinical practice continues to be predominantly characterized by the utilization of chemotherapy regimens. The development of anticancer therapies that are specifically targeted and precise in their action remains a significant challenge within this therapeutic domain. This study aims to discover new target genes and develop nucleic acid delivery systems. In this study, we identified the differentially expressed gene SDC1, which exhibited high levels of expression in TNBC and correlates with poorer overall survival trends through a comprehensive gene chip data screening analysis. The results of our analysis suggest a positive correlation between increased SDC1 expression levels and etoposide drug resistance in cases of TNBC. For mechanistic insights, scRNA-seq was employed to map SDC1-dependent alterations in the tumor microenvironment (TME) immune architecture. In view of this, the present study successfully constructed an in situ self-reactive gold nanocluster SDC1 shRNA-targeted nucleic acid delivery system in tumor cells by taking advantage of the reductive microenvironment at the tumor site, which significantly inhibited TNBC angiogenesis. This study elucidated the molecular mechanism by which SDC1 promotes tumor progression through multidimensional modulation of the TNBC microenvironment. It also proposed a bioinformatics-driven gene-targeting integrated platform for the rational design and delivery of gold nanocluster-based anticancer strategies.