RBCs as a Bioinspired Drug Delivery System for Co-delivery of Irinotecan and Nanoalumina Enhances Colorectal Cancer Therapy

Colorectal cancer (CRC) is a malignant epithelial tumor with high morbidity and mortality. In CRC treatment, irinotecan (CPT-11) as a chemotherapeutic drug is widely applied. However, its half-life is short, leading to large dosages and severe side effects. Red blood cells (RBCs) are biocompatible drug carriers with high capacity, avoiding premature drug degradation and achieving slow drug release. Nanoalumina (AN) is an emerging immune adjuvant that can enhance the immune response. Here, we used RBCs as carriers and absorbed AN to construct AN-CPT-11-RBCs. CPT-11 would induce tumor cell death, releasing much tumor antigen, while AN would activate immune cells to recognize newly released antigens and induce lymphocyte proliferation, enhancing the antitumor effect simultaneously. With loading amounts of 4 mg of CPT-11 and 3 mg of AN per 10⁹ RBCs, AN-CPT-11-RBCs had similar properties to natural RBCs. In vivo, AN-CPT-11-RBCs could circulate for 9 days and stimulate the proliferation of lymphocytes in the spleen and tumor tissue, having a higher tumor growth inhibition rate of 74.01% and a lower frequency of administration. In conclusion, AN-CPT-11-RBCs attain the co-delivery of CPT-11 and AN for the synergistic treatment of CRC.