The application of a dual-responsive mPEG-PLA-PHis-ss-PEI polypolymer (DRP/Res/siP) for the purpose of downregulating glycolytic pathways and upregulating mitochondrial OXPHOS in tumor cells resulted in a decrease in lactate production, an enhancement of the infiltration of CD8+ and CD4+ T lymphocytes, and improved anti-tumor efficacy when utilized in conjunction with PD-L1 silencing [88]. The gene discussed is CD274; the disease is neoplasm.