CEACAM5-Directed Tumor-Selective Delivery of DON Abolishes Gastrointestinal Toxicity and Synergizes with 5-FU in Colorectal Cancer

These PDX models were subsequently used to evaluate the synergistic antitumor efficacy and systemic biosafety of aCEA-Nano-DON in combination with 5-FU.Results: aCEA-Nano-DON exhibited excellent target specificity, selectively accumulating in CEACAM5-positive CRC cells while showing minimal uptake in normal intestinal tissues. In PDX models, aCEA-Nano-DON plus 5-FU achieved potent anti-tumor effects equivalent to free DON combination.

Importantly, the nanoplatform completely eliminated DON-induced systemic and gastrointestinal toxicity, preserving intestinal structure and hepatic and renal function.Conclusion: This targeted nanotherapy overcomes the clinical toxicity barrier of DON. aCEA-Nano-DON enables safe and effective combination with 5-FU, offering a promising translatable metabolic-chemotherapeutic strategy for CEACAM5-positive CRC treatment.