Inspired by the effective accumulation of P-TN-Dox@CM nanogel in the tumor region, we further evaluated the in vivo therapeutic effect on 4T1 orthotopic mammary tumor-bearing BALB/c mice. When the tumor volume reached about 60 mm 3 , the mice were randomly divided into the following ten groups: PBS as a control group (group a), PBS with 808 nm laser irradiation (group b, PBS+L), Dox (group c), P-Dox (group d), P-TN (group e), P-TN with 808 nm laser irradiation (group f, P-TN+L); P-TN-Dox (group g), P-TN-Dox with 808 nm laser irradiation (group h, P-TN-Dox+L), P-TN-Dox@CM (group i), P-TN-Dox@CM with 808 nm laser irradiation (group j, P-TN-Dox@CM+L). At 24 h post intravenous injection of different therapeutic agents, mice in group b, f, h, and j were irradiated by 808 nm laser for 15 min (0.8 mW cm -2 ). The tumor volumes and body weights of mice were measured every other day in the following two weeks, wherein the tumor volumes were normalized against their initial values (day 0) to assess the growth behaviors. At day 14, the tumors and major organs of mice from different groups were dissected and collected. As given in Figure , same with the PBS control group (group a), the tumors in the group b (PBS+laser) and group e (P-TN) grew dramatically during the treatment, suggesting neither 808 nm laser nor P-TN without irradiation had prominent influence on tumor growth. Albeit clinically approved, the commercial Dox (group c) only postponed the tumor progression moderately. The insufficient inhibition effect was likely due to the inadequate intratumoral accumulation and rapid blood clearance of free dox. The tumors of mice inoculated with P-Dox (group d) and P-TN-Dox without laser irradiation (group g) showed similar growth behaviors as the dox (group c) with partially inhibiting the tumor growth. After cloaking cancer cell membrane onto the surface of P-TN-Dox, the resultant P-TN-Dox@CM without laser irradiation (group i) showed a relatively higher chemotherapy efficiency caused by the homologous targeting effects. When combination therapy of P-TN-Dox plus laser irradiation (group h) was employed to mice, the tumor growth was significantly suppressed with a tumor growth inhibition (TGI) value of 78.44%, higher than that of the P-TN exposed to laser irradiation (group f, PTT alone), and P-TN-Dox without laser irradiation (group g, chemotherapy alone), indicating the significant synergistic effect of the P-TN-Dox-mediated chemo-photothermal therapy. Of note, the tumors of mice treated with P-TN-Dox@CM plus laser irradiation (group j, combination therapy) gained the highest inhibition efficiency with an almost complete tumor eradication (TGI = 92.9%), which should be attributed to the source 4T1 cancer cell membrane proteins-induced homologous targeting accumulation and retention of the P-TN-Dox@CM nanogels in the tumor sites, thus enhancing the synergistic therapeutic effects. The digital photographs and mass of the tumors eviscerated from mice also validated the superiority of synergistic chemo-PTT cotherapy with P-TN-Dox@CM nanogels in tumor growth restraint (Figure and). Hematoxylin-eosin (H&E) staining of tumor sections demonstrated that most of the tumor cells were severely destroyed and became necrotic in the group of P-TN-Dox@CM plus laser irradiation (group j), while tumor cells widely or partly maintained their normal histological morphology in other groups (Figure ), further demonstrating the group of P-TN-Dox@CM plus laser irradiation had the greatest therapeutic effect in all groups. Consequently, the satisfactory antitumor efficiency of P-TN-Dox@CM nanogels with NIR could be ascribed to the effectual synergism cooperation of Dox-mediated cytotoxicity and TN-mediated phototoxicity, as well as the source tumor cell membranemediated homologous targeting effects.