在癌症治疗中，药物传递系统（DDS）已被广泛研究，以实现在肿瘤部位的选择性药物积累。然而，DDS仍然存在一个主要缺点，即需要多步骤进程进行胞内传递，导致药物传递的效率低。为了克服这个问题，我们最近报道了一种分子块（MB），它使用去氧胆酸（DCA）在癌症微环境中破坏癌细胞膜。然而，MB即使在中性pH下也表现出相当的细胞毒性，可能是由于DCA的结构疏水性质所致。在此，我们重点考虑选择最适合MB的胆汁酸，该胆汁酸具有对癌症微环境高度敏感的特性，而在中性pH下没有细胞毒性。在中性pH（pH = 7.4）和癌症酸性环境（pH = 6.3-6.5）下评估了DCA，降去氧胆酸（CDCA），胆酸（CA）和熊去氧胆酸（UDCA）等游离胆汁酸的细胞生存率。 UDCA在pH = 7.4的半数抑制浓度（IC50）值表现出大约7.5倍于pH = 6.3的IC50值差异，而其他胆汁酸在相同的pH下的IC50值差异则少于4倍。生物相容的聚乙烯醇（PVA）被UDCA功能化（PVA-UDCA）以实现对癌症微环境更高灵敏度，而在中性pH下没有细胞毒性。重要的是，通过PVA-UDCA处理，在pH = 6.5时观察到56％的胰腺癌细胞死亡，而在中性pH下仅检测到10％。然而，无论pH条件如何，PVA-DCA表现出几乎相同的癌症细胞死亡特性。这些结果表明，PVA-UDCA显示出用于新类MB的巨大潜力。

In cancer therapy, a drug delivery system (DDS) has been widely studied to achieve selective drug accumulation at the tumor site. However, DDS still has a major drawback in that it requires multistep processes for intracellular delivery, resulting in low efficiency of drug delivery. To overcome this problem, we recently reported a molecular block (MB) that disrupts cancer cell membranes in the cancer microenvironment using deoxycholic acid (DCA). However, the MB showed considerable cytotoxicity even at neutral pH, possibly due to the structural hydrophobic property of DCA. Herein, we focused on selecting the most suitable bile acid for an MB that possessed high responsiveness to the cancer microenvironment without cytotoxicity at neutral pH. Cell viabilities of the free bile acids such as DCA, chenodeoxycholic acid (CDCA), cholic acid (CA), and ursodeoxycholic acid (UDCA) were evaluated at neutral pH (pH = 7.4) and a cancer acidic environment (pH = 6.3-6.5). The half-maximal inhibition concentration (IC50) value of UDCA at pH = 7.4 showed an approximately 7.5-fold higher IC50 value than that at pH = 6.3, whereas the other bile acids yielded less than a 4-fold IC50 value difference between the same pHs. Biocompatible poly(vinyl alcohol) (PVA) was functionalized with UDCA (PVA-UDCA) for the synthesis of higher responsiveness to the cancer microenvironment without cytotoxicity at neutral pH. Importantly, 56% pancreatic cancer cell death was observed at pH = 6.5, whereas only 10% was detected at neutral pH by the PVA-UDCA treatment. However, PVA-DCA indicated almost the same cancer cell death property, independent of pH conditions. These results suggest PVA-UDCA shows great potential for a new class of MB.