Colorectal cancer (CRC) is a heterogeneous disease with high incidence and mortality worldwide. The efficacy of conventional CRC chemotherapy is hampered by poor drug solubility and bioavailability and suboptimal pharmacokinetic profiles. In this work, camptothecin (CPT), a potent anticancer drug, was loaded into an amphiphilic chitosan modified with PEG and oleic acid, to reduce CRC progression after oral administration. While CPT-loaded micelles presented anticancer activity against HCT116, Caco-2 and HT29 CRC cell lines in vitro, empty micelles demonstrated a safe profile when incubated with human blood cells and colorectal cancer cell lines. In a more complex 3D CRC multicellular spheroid model, CPT-loaded micelles also exhibited a significant effect on the spheroid's metabolic activity and size reduction. Remarkably, in vivo studies performed in a HCT116 xenograft model, showed a significant reduction on the tumor growth during and after treatment with CPT-loaded micelles. Moreover, in a more biological relevant in vivo model of chemically-induced CRC, orally administered CPT-loaded micelles demonstrated a significant reduction on tumor incidence and inflammation signs. The findings here reported indicate that CPT-loaded into chitosan-based micelles, by improving drug solubility, alongside its safety profile for normal tissues, may have a promising role CRC chemotherapy.

结直肠癌（CRC）是一种异质性疾病，在全球范围内具有高发病率和死亡率。常规 CRC 化疗的疗效受到药物溶解度和生物利用度差以及药代动力学曲线欠佳的阻碍。在这项工作中，一种有效的抗癌药物喜树碱 (CPT) 被加载到用 PEG 和油酸修饰的两亲壳聚糖中，以减少口服后 CRC 的进展。而载有 CPT 的胶束在体外对 HCT116、Caco-2 和 HT29 CRC 细胞系表现出抗癌活性，当与人类血细胞和结肠直肠癌细胞系一起孵育时，空胶束表现出安全的特性。在更复杂的 3D CRC 多细胞球体模型中，装载 CPT 的胶束也对球体的代谢活性和尺寸减小有显着影响。值得注意的是，在 HCT116 异种移植模型中进行的体内研究显示，在用 CPT 加载的胶束治疗期间和之后，肿瘤生长显着减少。此外，在更生物学相关的体内在化学诱导的 CRC 模型中，口服负载 CPT 的胶束显示肿瘤发病率和炎症迹象显着降低。此处报道的研究结果表明，通过提高药物溶解度以及其对正常组织的安全性，将 CPT 加载到基于壳聚糖的胶束中，可能对 CRC 化疗具有良好的作用。