A new acid-sensitive drug-delivery nanocarrier has been developed for tumour targeting. The self-assembling co-polymer stearoyl–PEG–poly-sulfadimethoxine methacrylate (stearoyl–PEG–polySDM) was prepared to obtain micelles with responsive behaviour in the physiopathologic pH range. Stearoyl–PEG–polySDM was synthesised using a multi-step procedure that includes pH-sensitive sulfadimethoxine methacrylate polymerisation by AGET-ATRP at the amino terminal side of stearoyl–PEG–NH2. Chemical analysis showed that the stearoyl–PEG–polySDM co-polymer contained a mean of seven methacryloyl sulfadimethoxines per molecule. Potentiometric and turbidimetric analyses showed that stearoyl–PEG–polySDM has an apparent pKa of 7.2 and a cloud point at pH 7.0. In water at pH 7.4, the co-polymer assembled spontaneously into 13.2 ± 3.1 nm micelles with a critical micelle concentration (CMC) of 36 μM. Cell-culture studies showed that the material was more biocompatible with respect to the control Brij-700®. The paclitaxel loading capacity of the micelles was 3.25 ± 0.25% (w/w, %). The colloidal formulations were stable at pH 7.4 for several hours, while at pH 6.5, they rapidly rearranged and aggregated. Fluorescence spectroscopic and cytofluorimetric studies showed that the incubation of MCF-7 tumour cells with fluorescein-labelled stearoyl–PEG–polySDM at pH 6.5 resulted in massive time-dependent cell association, while the incubation at pH 7.4 showed significantly lower cell interaction. Confocal microscopy confirmed that at pH 6.5, the micelles are taken up by cells and that the fluorescein-labelled stearoyl–PEG–polySDM is distributed into the cytosol. At pH 6.5, paclitaxel-loaded stearoyl–PEG–polySDM micelles had a higher cytotoxic effect than the micelles incubated at pH 7.4. The former displayed similar cytotoxic activity to free paclitaxel.