A pH-responsive DNAsome derived from the amphiphilicity-driven self-assembly of DNA amphiphile containing C-rich DNA sequence is reported. The acidification of DNAsome induces a structural change of C-rich DNA from random coil to an i-motif structure that triggers the disassembly of DNAsome and its subsequent morphological transformation into an open entangled network. The encapsulation of a hydrophobic guest into the membrane of DNAsome and its pH-triggered release upon acidification of DNAsome is also demonstrated. [ABSTRACT FROM AUTHOR]