Benzobisthiazole polymer nanocarriers for temperature-responsive controlled drug release and synergistic chemo-photothermal therapy

• Biodegradable benzobisthiazole polymer with high photothermal efficiency and aqueous dispersibility. • Lauroyl chains enable heat-triggered phase transition for controlled drug release under NIR. • Synergistic chemo-photothermal therapy enhances apoptosis and ROS in osteosarcoma. • Benzobisthiazole polymer shows good biocompatibility and tumor suppression. Photothermal therapy has emerged as a promising anticancer strategy due to its non-invasiveness, spatial precision, and low risk of inducing drug resistance. However, the development of photothermal agents that integrate efficient synthesis, high photothermal conversion, good biocompatibility, and controlled drug-release capability remains a significant challenge. Herein, a benzobisthiazole-based polymer (DPDMN) was synthesized via a click condensation reaction and subsequently functionalized with lauroyl chloride to obtain DPDMN-DC. This acylation step introduces hydrophobic alkyl chains that enable a laser-triggered phase-transition, providing a controllable drug release. Doxorubicin (DOX) was loaded via hydrophobic interactions to form DPDMN-DC-DOX nanocomplex. The resulting nanocomplex exhibits favorable characteristics including small size, excellent aqueous dispersibility, high photothermal conversion efficiency, and biodegradability. More importantly, the temperature-responsive property of lauroyl chains allows precise, heat-triggered DOX release under near-infrared irradiation. Biological evaluations demonstrated that DPDMN-DC-DOX effectively suppresses osteosarcoma progression by enhancing intracellular reactive oxygen species generation and inducing apoptosis, while maintaining good biocompatibility. Compared to the DPDMN-DC, DPDMN-DC-DOX shows significantly enhanced antitumor efficacy, attributed to the synergistic effect of photothermal ablation and chemotherapy. In summary, this work presents a rationally designed benzobisthiazole polymer nanocarriers with temperature-responsive controlled drug release behavior, offering a promising platform for synergistic chemo-photothermal cancer therapy.