Background: Many cancer cell lines, such as Hepa 1-6 (liver), A549 (lung), Hela (cervical), and MCF7 (breast), do not overexpress tyrosinase, an enzyme needed to activate the prodrug quercetin into its active form, o-quinone. In addition, these cancers do not rely on extracellular tyrosine for growth, as they can produce small amounts intracellularly. Methods: We investigate two therapeutic strategies using nanocapsules containing polyhemoglobin–tyrosinase (PolyHb–Tyr–nano) for action on (1) the intracellular activation of quercetin to o-quinone and (2) the depletion of intracellular tyrosine. We applied these strategies to the four cell lines listed above. Results: (1) PolyHb–Tyr–nano activates quercetin intracellularly, increasing o-quinone levels and reducing cancer cell viability. (2) PolyHb–Tyr–nano alone suppresses tumor growth by lowering intracellular tyrosine. Furthermore, PolyHb–Tyr–nano shows selective cytotoxicity, with an LD50of 0.7808 mg/mL in Hepa 1-6, compared with an extrapolated LD50of 84,181 mg/mL in the normal liver cells. In contrast, quercetin activation results in an LD50of 2.73 mg/mL in Hepa 1-6 and 74.18 mg/mL in normal hepatocytes. Conclusions: PolyHb–Tyr–nano offers dual therapeutic functions: (1) quercetin prodrug activation and (2) intracellular tyrosine depletion.
背景：许多癌细胞系，如Hepa 1-6（肝）、A549（肺）、Hela（宫颈）和MCF7（乳腺），并不高表达酪氨酸酶——一种将前药槲皮素激活为活性形式邻醌所需的酶。此外，这些癌细胞不依赖细胞外酪氨酸生长，因为它们能在细胞内少量合成。方法：我们研究了两种使用含聚血红蛋白-酪氨酸酶的纳米胶囊（PolyHb–Tyr–nano）的治疗策略，作用于：（1）槲皮素在细胞内激活为邻醌；（2）细胞内酪氨酸的耗竭。我们将这些策略应用于上述四种细胞系。结果：（1）PolyHb–Tyr–nano在细胞内激活槲皮素，提高邻醌水平并降低癌细胞活力；（2）PolyHb–Tyr–nano单独通过降低细胞内酪氨酸抑制肿瘤生长。此外，PolyHb–Tyr–nano显示出选择性细胞毒性，在Hepa 1-6细胞中的LD50为0.7808 mg/mL，而在正常肝细胞中外推的LD50为84,181 mg/mL。相比之下，槲皮素激活在Hepa 1-6细胞中的LD50为2.73 mg/mL，在正常肝细胞中为74.18 mg/mL。结论：PolyHb–Tyr–nano具有双重治疗功能：（1）激活槲皮素前药；（2）耗竭细胞内酪氨酸。
肿瘤(癌症)患者之家