Enhancing the regulatory effect of LY9 on breast cancer microenvironment through a nanodelivery system

The tumor microenvironment (TME) is closely related to breast cancer (BC) tumorigenesis and progression. However, the specific composition of TME remains largely elusive. Thus, we aimed to identify TME-related biomarkers in BC. Through comprehensive screening, five promising genes were identified, which significantly predicted favorable survival outcomes and demonstrated consistent antigen presentation capability. Among these, LY9 emerged as the most inhibitory factor for BC. The findings indicated LY9 is a potential factor, regulating tumor immune activities in BC patients, which is strongly associated with several several tumor-infiltrating immune cells(TICs). To further validate the role of LY9 in inhibiting tumor cell formation, we conducted a series of experiments, including cloning formation experiments, scratch assays, and animal subcutaneous tumor formation experiments. A hybrid nanodelivery system composed of DSPE-PEG and DOTAP was used in this study. The results show that siLY9 encapsulated by nanoparticles (Nano-siLY9) can be accurately delivered to the vicinity of tumors, and significantly improving the knockout efficiency of LY9 gene and promoting the growth of tumors. These results reveal that LY9 not only could serve as an indicator for TME remodeling, but also acts as a suppressor of breast cancer cell proliferation. Importantly, compared with free siLY9, Nano-siLY9 has stronger biological effects without increasing biological toxicity. Hence, this finding may pave the way for decoding the complicated interaction between tumor cells and TME as well as for providing new avenues for therapeutic intervention in breast cancer.