Hou Ping, Xie Lingeng, Zhang Ludan, Du Xin, Zhao Decai, Wang Yuguang, Yang Nailiang, Wang Dan
State Key Laboratory of Biochemical Engineering Key Laboratory of Biopharmaceutical Preparation and Delivery Institute of Process Engineering, Chinese Academy of Sciences, 1 North 2nd Street, Zhongguancun, Haidian District, Beijing, 100190, P. R. China.
University of Chinese Academy of Sciences, 19 A Yuquan Road, Beijing, 10049, P. R. China.
Angew Chem Int Ed Engl. 2025 Jan 10;64(2):e202414370. doi: 10.1002/anie.202414370. Epub 2024 Nov 18.
Effective intratumoral drug penetration is pivotal for successful cancer treatment. However, due to the disrupted capillary networks and poor perfusion in solid tumors, there exist challenges to realize autonomous directional drug penetration and controlled drug release within the tumor. Considering the specificity of glucose within tumor tissue, we draw inspiration from nature and engineer asymmetrical hollow structures exhibiting chemotaxis towards high glucose levels. By incorporating multiple shells into these structures, we enhance the local chemical concentration gradients, thereby improving cellular uptake and precise targeting. The advantages of anisotropic hollow multishell structure (a-HoMS) can be reflected from the diffusion coefficient and directivity, which increase by 73.4 % and 273 % respectively compared to conventional isotropic hollow spheres, achieving the most linear movement while ensuring the speed of movement. Furthermore, the multi-level porosity and temporal-spatial order of a-HoMS enable sequential drug delivery that inhibits angiogenesis with inducing cell apoptosis. After the eradication of localized tumor cells, the a-HoMS can automatically migrate to the alive tumor cells under the glucose gradient, inducing another cycle of drug delivery and chemotaxis, resulting in excellent antitumor efficacy. These anisotropic HoMS demonstrate intelligence, adaptability, and precision in tumor therapy, providing valuable insights for programmable treatment within tissues.
有效的肿瘤内药物渗透对于成功的癌症治疗至关重要。然而，由于实体瘤中毛细血管网络紊乱和灌注不良，在肿瘤内实现自主定向药物渗透和可控药物释放存在挑战。考虑到肿瘤组织内葡萄糖的特异性，我们从自然界汲取灵感，设计出对高葡萄糖水平表现出趋化性的不对称空心结构。通过在这些结构中加入多层壳，我们增强了局部化学浓度梯度，从而提高了细胞摄取和精确靶向性。各向异性空心多壳结构（a-HoMS）的优势可以从扩散系数和方向性上体现出来，与传统的各向同性空心球相比，扩散系数和方向性分别提高了73.4%和273%，在确保移动速度的同时实现了最线性的移动。此外，a-HoMS的多级孔隙率和时空有序性能够实现顺序给药，通过诱导细胞凋亡来抑制血管生成。在根除局部肿瘤细胞后，a-HoMS可以在葡萄糖梯度作用下自动迁移到存活的肿瘤细胞，引发另一轮药物递送和趋化作用，从而产生优异的抗肿瘤疗效。这些各向异性的HoMS在肿瘤治疗中展现出智能性、适应性和精确性，为组织内的可编程治疗提供了有价值的见解。
