Supramolecular Visualized Chemotherapy Based on OxPt-TTVP@CB[8]: Activating Oxidative Damage to Induce ICD for...

Chemotherapy with spatiotemporal precision and noninvasiveness offers a new treatment strategy for colorectal cancer. However, this therapy still has shortcomings in how chemotherapeutic drugs are visualized and their antitumor effects. To improve the therapeutic efficacy, we have fabricated a facile host-guest complex (OTC) that resorts to noncovalent interactions among oxaliplatin (OxPt), photosensitizer (TTVP), and cucurbit[8]uril (CB[8]). OTC significantly enhanced the aggregation-induced emission (AIE) effect of TTVP. We further confirmed that OTC targeted aggregation in tumors by xenograft nude mouse models. This enabled the functions of tracing the chemotherapeutic drug, localizing the tumor, and targeting tumor accumulation. The tumor growth inhibition value (TGI) was 68.01% in the OTC group. Importantly, OTC-regulated drug release was observed through spermidine exchange in vitro and in vivo. The toxicity of OTC to normal cells under light-avoidance conditions was significantly less than that of conventional chemotherapeutic agents (OxPt), implying that OTC exhibited high efficacy and low toxicity. Upon light irradiation, OTC generated reactive oxygen species (ROS), leading to oxidative damage, while MDA levels were elevated, but SOD and CAT activities were reduced. We found that HMGB1, CRT, and ATP in the OTC-treated group increased by 87.20, 43.30, and 34.60% in vitro, respectively, compared with the control group. Transcriptomic analysis revealed upregulation of pathways related to immune activation, suggesting that OTC treatment primed the tumor for immunotherapy. The possible biological mechanism behind this was that OTC activated oxidative damage to induce immunogenic cell death (ICD). Overall, OTC offers a simple, visual, and highly efficient method for transporting platinum to improve chemotherapy. It also provides a novel strategy for combining chemotherapy and immunotherapy in solid tumors.