癌症治疗需要新的策略来开发具有改善疗效的药物载荷纳米载体。在本文中，我们报告了一种新颖的药物输送纳米系统，它包括将化疗药物多西紫杉醇（DTX）封装在一种弹性蛋白样重组聚合物（ELR）载体中，同时与Akt激酶的小肽抑制剂重组融合。这种联合方法还通过化学共轭的针对CD44肿瘤标记物的DNA适配体精确靶向结直肠癌细胞。发现这种直径为53纳米的双重方法纳米系统与内皮细胞相比，对体外结直肠癌细胞的细胞存活率（2.5%存活）和增殖选择性影响更大（50%存活），并且可以引发细胞凋亡和坏死介导的细胞死亡。我们的研究结果还表明，这种纳米混合颗粒在生理条件下保持稳定，触发持续的药物释放，并在系统静脉注射后具有适当的药代动力学特性。在小鼠结直肠癌模型中的体内实验表明，这些双重方法纳米混合物显著减少了结直肠道中肿瘤息肉的数量。此外，高级纳米混合物的系统管理通过改善胃肠道窝样和组织结构来促进组织恢复。总的来说，这些发现表明我们的先进双重方法纳米系统策略使我们能够在癌细胞中成功实现化疗药物的可控释放，并在结直肠癌治疗中具有良好的潜力。版权所有©2023，由Elsevier B.V.出版。

New strategies to develop drug-loaded nanocarriers with improved therapeutic efficacy are needed for cancer treatment. Herein we report a novel drug-delivery nanosystem comprising encapsulation of the chemotherapeutic drug docetaxel (DTX) and recombinant fusion of a small peptide inhibitor of Akt kinase within an elastin-like recombinamer (ELR) vehicle. This combined approach is also precisely targeted to colorectal cancer cells by means of a chemically conjugated DNA aptamer specific for the CD44 tumor marker. This 53 nm dual-approach nanosystem was found to selectively affect cell viability (2.5 % survival) and proliferation of colorectal cancer cells in vitro compared to endothelial cells (50 % survival), and to trigger both apoptosis- and necrosis-mediated cell death. Our findings also show that the nanohybrid particles remain stable under physiological conditions, trigger sustained drug release and possess an adequate pharmacokinetic profile after systemic intravenous administration. In vivo assays showed that these dual-approach nanohybrids significantly reduced the number of tumor polyps along the colorectal tract in a murine colorectal cancer model. Furthermore, systemic administration of advanced nanohybrids induced tissue recovery by improving the morphology of gastrointestinal crypts and the tissue architecture. Taken together, these findings indicate that our strategy of an advanced dual-approach nanosystem allows us to achieve successful controlled release of chemotherapeutics in cancer cells and may have a promising potential for colorectal cancer treatment.Copyright © 2023. Published by Elsevier B.V.