Abstract: To improve the therapeutic effect of cisplatin and reduce its side effects, a multifunctional drug delivery system with targeted and chemo-photothermal effect was constructed.Using polyethylene glycol polylactic acid block copolymer as a carrier, nanoparticles loaded with antitumor drug cisplatin and photosensitizer indocyanine green were prepared by ultrasonic emulsification, and the surface was then modified by cetuximab to prepare cetuximab-decorated and near-infrared (NIR)-activated nanoparticles (CPINPs).The physicochemical properties were characterized by mean particle size, Zeta potential, mAb conjugating rate and photothermal effect; the in vitro cell uptake was measured by laser confocal microscopy; and the in vitro antitumor activity was evaluated by CCK8 assay.The results indicated that CPINPs had mean particle diameter of (263.9 ± 3.73) nm, polydispersity index of 0.18 ± 0.03, Zeta potential of -(23.43 ± 0.42) mV, and cetuximab conjugating rate of (44.0 ± 1.72)%.The in vitro photothermal experiments showed that CPINPs upon NIR irradiation induced a photothermal effect, thus destroying the tumor cells. The in vitro cell uptake experiments demonstrated that NIR irradiation could promote cell uptake, and that more CPINPs were effectively internalized into A549 cells. The in vitro cytotoxicity test indicated that CPINPs treated with NIR irradiation had the effect of combined chemo-photothermal therapy, leading to higher cytotoxicity than that of free cisplatin or treatment without NIR, with IC₅₀ values being (8.67 ± 0.04) μmol/L for 24 h incubation.To sumup the multifunctional drug delivery system constructed in the current work expected to be a more efficient targeted therapy strategy for lung cancer.