ABSTRACT Chitosan (CTSN), a cationic biopolymer was used to prepare Ion pair self-assembly (IPSAM) with (phenylthio)acetic acid (PTA) as hydrophobic counter ion which is responsive to temperature and oxidation. The IPSAM was formed when the amino to carboxylic group molar ratio was 1/9 ~ 4/6. CTSN/PTA IPSAM was found as sphere-like nanoparticles whose diameter was 30–50 nm on TEM image. The ion pair showed the upper critical solution temperature (UCST) that increased with increasing PTA content and decreased when PTA of the ion pair was oxidized by H2O2. The ion pair exhibited amphiphilic property which was responsible for interface activity which decline upon the oxidation of the PTA. The surface tension was low for the ratio of CTSN/PTA (3/7), which made the 3/7 ratio suitable for further studies. The ionic interaction between CTSN and PTA and the oxidation of PTA were confirmed by FT-IR spectroscopy. The payload’s release (i.e. Nile red) in IPSAM was constrained below the UCST but it was prompted above the phase transition temperature possibly due to the disassembly of the IPSAM and PTA oxidation. The release was found to be higher in tumor environment temperature in the presence of H2O2 indicating the release was dependent on temperature and oxidation.