LAUSR

ABSTRACT Thermoresponsive and acid-cleavable amphiphilic block copolymers poly(N-isopropylacrylamide)-acetal-poly(4-substituted-ε-caprolactones) (PNiPAAm-a-PXCLs) containing an acidic-cleavable acetal linkage at the junction between the temperature-sensitive hydrophilic PNiPAAm and the degradable hydrophobic block PXCL were synthesized through ring-opening polymerization and electrophilic addition reactions. These polymer solutions showed reversible changes in optical properties and a lower critical solution temperature in the range of 32.0–46.4°C. The copolymers formed micelles in aqueous solution with critical micelle concentrations in the range of 0.83–15.95 mg L−1 had hydrodynamic sizes of <200 nm and were spherical. Under the combined stimulation of temperature and pH, the micellar nanoparticles could be dissociated; the loaded molecules could be released from the assemblies more efficiently than that under only one stimulus or without stimulus. In addition, the nanoparticles exhibited low toxicity against human cervical cancer (HeLa) cells at concentrations ≤1000 µg mL−1. Doxorubicin-loaded PNiPAAm11-a-PCL28 micelles also effectively inhibited the proliferation of HeLa cells with a half-maximal inhibitory concentration (IC50) of 1.60 µg mL−1. GRAPHICAL ABSTRACT