An Injectable Photothermal Responsive Liposome Hydrogel Co-Loaded with Bufalin, Apatinib, and IR820 for Inhibiting Postoperative Recurrence of Colon Cancer

Background: Colon cancer ranks as the third most common malignant tumor globally. Due to incomplete surgical resection and the multidrug resistance of tumor cells, it exhibits a high postoperative recurrence rate. Consequently, there is an urgent need to develop novel therapeutic strategies to inhibit postoperative recurrence of colon cancer. Methods: Thermosensitive liposomes (Bu&Ap-Lip) co-loaded with bufalin (Bu) and apatinib (Ap) were prepared via the thin-film hydration method, with optimization of Prescription Processes. Bu&Ap-Lip was co-encapsulated with new indocyanine green (IR820) within an injectable PLGA-PEG-PLGA hydrogel, establishing a photothermally responsive composite hydrogel (Bu&Ap-Lip@IR820 Gel). The system characterized the physicochemical properties, rheological characteristics, and drug release behavior of the hydrogel, and further evaluated its in vitro antitumor activity and in vivo efficacy against postoperative recurrence of colon cancer. Results: Bu&Ap-Lip@IR820 Gel demonstrated excellent injectability and photothermally responsive drug-release properties. In vitro cellular experiments demonstrated that Bu&Ap-Lip@IR820 Gel effectively inhibited tumor cell migration, invasion, and angiogenesis. In vivo studies revealed that this liposome hydrogel prolonged local drug retention. When combined with near-infrared light irradiation, Bu&Ap-Lip@IR820 Gel significantly suppressed tumor recurrence while exhibiting favorable in vivo biocompatibility. Conclusion: This study developed a NIR-responsive composite liposome hydrogel integrating Bu multi-targeted antitumor properties, Ap anti-angiogenic effects, and IR820 photothermal therapeutic advantages. Through near-infrared responsiveness, it achieves localized precision drug release, effectively suppressing postoperative recurrence. This provides a novel and promising strategy for the clinical prevention and treatment of colon cancer recurrence.