Polymers designed to change their conformation via a phase transition triggered by acidic cleavage of a hydrophobic side-chain have been synthesized and characterised. The new materials were prepared by co-polymerising N-isopropylacrylamide with an acetal-containing pH-sensitive monomer N-(2-(2,4,6-trimethoxyphenyl)-1,3-dioxan-5-yl)acrylamide (TMPDA) and then grafting the resultant linear co-polymers to branched poly(ethyleneimine). The final three-component polycations exhibited Lower Critical Solution Temperature (LCST) behaviour. The structures of these polymers, their solution behaviour and their self-association were characterized by DLS and TEM in water and buffer solutions. The acid-triggered hydrolysis of trimethoxybenzeneacetal side-chains on the poly(N-isopropylacrylamide-co-TMPDA) grafts resulted in changes in lower critical solution temperatures and in solution self-assembly; thus in effect creating an ‘isothermal’ phase transition. The changes in polymer conformation, at acidity levels corresponding to those in cell endosomes, offer promise for these polymers to act as controlled release materials.