Therapeutic efficacy arises through some interlinked mechanisms: HSPD1 silencing reduces HSP60 protein levels, thereby derepressing p53-mediated tumor suppression, p53 activation transcriptionally represses glycolytic effectors HK2, PKM2, and LDHA to impair Warburg metabolism, and metabolic control of proliferation, establishing siRNA@EVs as precision nanotherapy targeting PCa's metabolic-transcriptional axis. Here, LDHA is linked to posterior cortical atrophy.