In recent years, synergistic chemo-photothermal therapy has revealed promising potential in treatments against various kinds of cancer. However, the development of superb photothermal agents with high drug loading capacity is still highly required. In this work, a hollow mesoporous polyaniline nanoparticle (HPANI NP) has been developed for encapsulating chemotherapeutic drug doxorubicin (DOX) with an remarkable drug loading content as high as 37.5%. Additional PEG modification endowed the drug-loaded HPANI NPs with improved water-dispersibility and bioavailability. Such PEG-HPANI-DOX NPs exhibited strong NIR absorbance and robust photothermal conversion capacity, exhibiting highly efficient synergistic cancer treatment. More interestingly, the responsively released DOX molecules could emit strong red fluorescence, which could be employed to monitor the cellular endocytosis and drug release profile of PEG-HPANI-DOX NPs. Finally, the as-fabricated NPs showed good biocompatibility and low toxicity, serving as a promising nanoagent for highly efficient drug delivery and cancer combination therapy. (C) 2021 The Chemical Industry and Engineering Society of China, and Chemical Industry Press Co., Ltd. All rights reserved.