The dark cytotoxicity and antiproliferative effects of the nanogels were assessed using (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) standard assay. As shown in Figure , the Dox-free nanogels (PNA, P-TN, and P-TN@CM) exhibited trifling dark cytotoxicity even when the concentration of nanogels was increased to 500 μg mL -1 , demonstrating the low cytotoxicity and good biocompatibility of the nanocarriers. Upon NIR irradiation (Figure ), neither PNA nanogels nor 808 nm laser alone showed apparent cytotoxicity against 4T1 tumor cells, whereas, the cell viability of 4T1 tumor cells treated with TN-loaded nanogels (P-TN and P-TN@CM) displayed a striking drop due to the outstanding photothermal effects induced by TN-loaded nanogels. In addition, the cytotoxicity to 4T1 tumor cells enhanced when the dose of TN-loaded nanogels increased or the laser power density elevated (Figure ). Consequently, the TN-loaded nanogels (P-TN and P-TN@CM) are promising photothermal candidates for ablating tumor cells. Furthermore, the synergistic chemo-photothermal therapeutic effects of Dox and TN co-loaded nanogels were investigated (Figure ). Free Dox exhibited a stronger dark cytotoxicity than the P-TN-Dox or P-TN-Dox@CM nanogels without laser irradiation since free Dox could diffuse into nuclei directly. The P-TN-Dox@CM nanogels had a half maximal inhibitory concentration (IC50) of 6.41 μg mL -1 in the absence of NIR irradiation, which was lower than that of P-TN-Dox nanogels (IC50 = 12.11 μg mL -1 ). The enhanced dark cytotoxicity could be ascribed to the elevated cellular uptake assisted by 4T1 tumor cell membrane proteins. Remarkably, the P-TN-Dox@CM+L group offered the highest antiproliferative effects with a IC50 value of 2.14 μg mL -1 , which was 2.99-and 2.78-fold lower than that of P-TN-Dox@CM group and P-TN@CM+L group, respectively. Overall, the chemotherapy combined with photothermal therapy (P-TN-Dox@CM+L) could give rise to a notable synergistic inhibition efficacy, superior than either sole-chemotherapy (P-TN-Dox@CM in dark) or sole-phototherapy (P-TN@CM+L). 4T1 cells with various concentrations of PNA, P-TN, and P-TN@CM nanogels under 808 nm laser irradiation (0.8 W cm -2 ) for 10 min (Concentration based on PNA). (d) In vitro cytotoxicity of 4T1 cells under different conditions for 48 h (Concentration based on Dox). "L" refers to 808 nm laser irradiation (0.8 W cm -2 for 10 min).