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pH-Induced Charge-Reversal Amphiphile with Cancer Cell-Selective Membrane-Disrupting Activity
Yincheng Chang1, Zehuan Huang1, Yang Jiao1
1Key Lab of Organic Optoelectronics & Molecular Engineering, Department of Chemistry , Tsinghua University , Beijing 100084 , China.
Abstract:
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.
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