Key Lab of Organic Optoelectronics & Molecular Engineering, Department of Chemistry , Tsinghua University , Beijing 100084 , China.
ACS Appl Mater Interfaces. 2018 Jun 27;10(25):21191-21197. doi: 10.1021/acsami.8b06660. Epub 2018 Jun 13.
A charge-reversal amphiphile exhibiting charge conversion from negative to positive induced by pH is reported. It selectively kills cancer cells through cell membrane disruption. This amphiphile comprising an alkyl chain and anionic headgroup of acid-labile β-carboxylic amide (C16N-DCA) was prepared. In the microenvironment of normal cells with pH 7.4, the negatively charged C16N-DCA exhibited considerably reduced cytotoxicity. However, in the acidic microenvironment of cancer cells with pH 6.5-6.8, the headgroup charge of C16N-DCA changed from negative to positive under hydrolysis of the acid-labile amide group. As a result, the generated cationic amphiphile displayed significant killing of cancer cells by disrupting their cell membranes. Such pH-selective cell killing bioactivity represents a new route of chemotherapy for anticancer strategies.
一种电荷反转两亲分子，通过 pH 值诱导从负电荷转换为正电荷，被报道。它通过破坏细胞膜选择性地杀死癌细胞。这种两亲分子由烷基链和带负电荷的酸不稳定β-羧酸酰胺（C16N-DCA）的阴离子头基组成。在正常细胞的微环境 pH 值为 7.4 时，带负电荷的 C16N-DCA 表现出明显降低的细胞毒性。然而，在 pH 值为 6.5-6.8 的癌细胞酸性微环境中，酸不稳定酰胺基团的水解导致 C16N-DCA 的头基电荷从负电荷变为正电荷。结果，所生成的阳离子两亲分子通过破坏细胞膜显著杀死癌细胞。这种 pH 选择性细胞杀伤生物活性为抗癌策略的化疗提供了新途径。
