By reducing the expression of pyruvate kinase isozyme M2 (PKM2) and hexokinase-2 (HK-2), SHK@Mn-TiO2 effectively inhibited glycolysis, thereby reversing the hypoxic tumor microenvironment (TME), as evidenced by a more than ∼50% decrease in hypoxia-inducible factor-1α (HIF-1α) and lactate (LA) levels compared with those of Mn-TiO2. The gene discussed is HK2; the disease is neoplasm.