Immediate tumor killing and long-term anti-tumor immunoreaction induced by Bufalin-loaded phototherapeutic Janus membrane in CRC postoperative therapy

Colorectal cancer (CRC) management is significantly hindered by the challenges of early detection and the high rates of recurrence and metastasis following surgery. Systemic postoperative therapies are frequently compromised by adverse effects and drug resistance. To address this, we engineered a localized and combinatorial platform by integrating Bufalin (BU), a potent anti-tumor agent from traditional Chinese medicine, into citric acid-based carbon dots modified with hyaluronic acid (BU-CDs_CA-HA), which were subsequently incorporated into a Janus-structured membrane. This design enabled robust adhesion to post-resection tumor sites, ensuring sustained local drug release and spatially confined photothermal/photodynamic therapy (PTT/PDT) while effectively sparing adjacent healthy tissues from thermal damage. Upon near-infrared (NIR) irradiation, the synergistic BU-PTT/PDT action induced potent immunogenic cell death (ICD), as evidenced by the release of damage-associated molecular patterns (DAMPs), thereby initiating a systemic anti-tumor immune response. Concurrently, BU down-regulated heat shock proteins (HSPs) and HIF-1α expression, leading to the suppression of tumor PD-L1 and effectively countering immune escape. In orthotopic and metastatic CRC mouse models, this multifunctional Janus membrane system demonstrated remarkable efficacy in preventing local recurrence and distant metastasis. This outcome was attributed to the concerted effect of immediate cytotoxic ablation and the elicited durable anti-tumor immunity. Our work presents a novel biomaterial-based strategy that enhanced the efficacy and safety of postoperative CRC treatment, offering a versatile platform for site-specific combination therapy.