In this study a novel class of pH-responsive polymers based on new substituted phenol monomers is presented. A judicious choice of the electron-withdrawing groups on the aromatic ring allowed modulation of both their pKa and hydrophobicity. Preliminary experiments using poly[2-((methacryloyloxy)ethyl-3-chloro-4-hydroxybenzoate)-r-(glycerol methacrylate)], poly(MCH-r-GMA), showed that the pKa of the MCH repeating units is in the 6.5–7 range, which opened the way for their application in the assembly of drug-delivery nanocarriers. These pH-responsive materials are unusual in that, unlike the systems based on organic amine frequently employed for this purpose, they possess hydrophilic behaviour in basic aqueous conditions, whilst they become hydrophobic upon acidification. Poly(MCH-b-PEGMA475) could be easily assembled in either stable micellar or polymersome nanocarriers by simply modifying the hydrophilic : hydrophobic balance of their block components. Interestingly, the size of poly(MCH-b-PEGMA475) nanoaggregates was found to be strongly pH-dependent, going from 32 nm at pH 7.4 to 120 nm at pH 5.5. Preliminary drug entrapment experiments showed a loading of tamoxifen model hydrophobic drug as high as 17–19% w/w, whilst as expected a significant amount of hydrophilic doxorubicin hydrochloride, 14% w/w, could be incorporated in polymersome poly(MCH-b-PEGMA475) nanocarriers.