An excellent drug delivery system should prevent the premature drug leakage during blood circulation while release drugs rapidly upon arrival at the specific pathological sites to ensure delivery specificity. The drug release behaviors of Dox from P-TN-Dox and P-TN-Dox@CM nanogels were investigated in a simulated physiological medium (PBS buffer with pH 7.4) and a simulated tumor tissue medium (PBS buffer with pH 5.0). As displayed in Figure , the cumulative release of Dox from P-TN-Dox nanogels in pH 5.0 was much higher than that in pH 7.4, signaling representative pH-responsive drug release behavior. For instance, when external temperature was 42 o C, the cumulative release of Dox from P-TN-Dox nanogels was only 29% in pH 7.4 after 48 h, whereas around 78% in pH 5.0. The low pH (pH 5.0) increased the protonation degree of the amino groups in Dox and carboxyl groups in nanogels, which led to the undermining of electrostatic interaction between positively charged Dox and carboxyl groups in nanogels as well as shrinkage of nanogels, thus drug release was improved. In addition, the cumulative drug release ratio increased with the elevation of temperature from 25 o C to 42 o C. This was likely owing to the elevated temperature weakened the hydrogen bonds between water molecules and nanogels, and impelled the volume phase transition from swelling state to shrinking state, thus the shrunken nanogels squeezed Dox out from P-TN-Dox nanogels. Meanwhile, since the drug desorption was an endothermic process, temperature elevation thus could also facilitate the drug release because of the dissociation of the electrostatic interactions between Dox molecules and nanogels at elevated temperature. Notably, the tumor cell membrane cloaking had negligible effect on the drug release characteristics of P-TN-Dox-CM nanogels (Figure ). Hence, the pH-and thermo-responsive controllable drug delivery system could efficiently remain stable and lessen premature drug leakage in the bloodstream, and achieve quick release locally in the acidic and heated tumor environment, which could minimize off-target effects and enhance therapeutic efficiency, thus providing great potentials for multi-stimuli-triggered precise antitumor therapy.