Abstract
Background: Immunotherapy resistance in ovarian cancer (OC) poses a significant clinical hurdle. This study aims to investigate the potential of NGR-modified biomimetic nanovesicles (NGR-BNVs) for delivering ALKBH5 siRNA to reverse this resistance. Methods: In vitro and in vivo experiments were conducted to assess the efficiency of NGR-modified nanovesicles in delivering ALKBH5 siRNA. OC cell proliferation was evaluated, and apoptosis induction was measured. A mouse xenograft model was utilized to examine the effects on tumor volume and metastasis. Tumor immune microenvironment (TIME) analysis was performed to determine changes in immune cell proportions and immunomodulatory factors. Results: NGR-modified nanovesicles effectively delivered ALKBH5 siRNA, leading to a significant inhibition of OC cell proliferation and apoptosis induction. Treated groups in the mouse xenograft model exhibited reduced tumor volume and decreased metastatic signals. Analysis of the immune microenvironment revealed an increased proportion of CD8(+) T cells, reduced Tregs and MDSCs, and notable changes in key immunomodulatory factors. Conclusion: This study highlights the potential of NGR-modified BNVs for overcoming immunotherapy resistance in OC by delivering ALKBH5 siRNA, resulting in modulation of the immune microenvironment and promising therapeutic outcomes.