中国科学院过程工程研究所王丹团队报道了具有趋化性的各向异性中空结构实现肿瘤内自主神经治疗。相关研究成果于2024年10月23日发表在《德国应用化学》。

高效的肿瘤内药物渗透是癌症治疗成功的关键。然而，由于实体瘤中毛细血管网络的破坏和灌注不良，在肿瘤内实现自主定向药物渗透和受控药物释放存在挑战。

考虑到肿瘤组织内葡萄糖的特异性，研究人员从自然界中汲取灵感，设计出不对称的中空结构，其表现出对高葡萄糖水平的趋化性。通过将多个壳结合到这些结构中，增强了局部化学浓度梯度，从而改善了细胞摄取和精确靶向。

各向异性空心多壳结构（a-HoMS）的优点可以从扩散系数和方向性上反映出来，与传统的各向同性空心球相比，分别提高了73.4%和265%，在保证运动速度的同时实现了最线性的运动。

此外，a-HoMS的多级孔隙率和时空顺序能够实现顺序药物递送，从而抑制血管生成并诱导细胞凋亡。在根除局部肿瘤细胞后，a-HoMS可以在葡萄糖梯度下自动迁移到活的肿瘤细胞中，诱导另一个药物递送和趋化循环，从而产生优异的抗肿瘤疗效。

这些各向异性HoMS展示了肿瘤治疗的智能性、适应性和精确性，为组织内的可编程治疗提供了宝贵的见解。

附：英文原文

Title: Anisotropic Hollow Structure with Chemotaxis Enabling Intratumoral Autonomic Therapy

Author: Nailiang Yang, Ping Hou, Lingeng Xie, Ludan Zhang, Xin Du, Decai Zhao, Yuguang Wang, Dan Wang

Issue&Volume: 2024-10-23

Abstract: 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 265% 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.

DOI: 10.1002/anie.202414370

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202414370