Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 29 Zhongguancun East Road, Beijing, 100190, PR China; CAS Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Beijing, 100190, PR China; College of Biomedical Engineering, Sichuan University, Chengdu, 610065, PR China.
Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 29 Zhongguancun East Road, Beijing, 100190, PR China; CAS Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Beijing, 100190, PR China.
Biomaterials. 2022 Apr;283:121472. doi: 10.1016/j.biomaterials.2022.121472. Epub 2022 Mar 16.
Microwave thermal therapy (MWTT) shows great prospect in cancer treatments due to its non-invasive or minimally invasive nature and deep penetration through the tissue. However, incomplete ablation and elevated expression of many pro-tumor angiogenesis after MWTT (e.g., vascular endothelial growth factor, VEGF) induced tumor recurrence still remains an obstacle, especially in some tumors prone to recurrence and metastasis, such as colorectal cancer. Herein, we propose a nanocapsule of covalent organic framework cladding metal organic framework (MOF@COF) with microwave (MW) thermal-dynamic sensitization and co-action of tumor anti-angiogenesis. The MOF of Bi-Mn-porphyrin (BM) is designed as MW sensitizer to generate cytotoxic O and heat for microwave dynamic therapy (MWDT) synergistic MWTT. The COF is covalently coated on BM for further augmenting these two sensitization properties, as well as loading hydrophobic inhibitor of Apatinib to downregulate the expression of VEGF for inhibiting tumor recurrence. Furthermore, the contained Bi and porphyrin endow system with CT and fluorescence imaging (FI) capabilities. In vivo experiments verify that this combination therapy significantly impairs the growth of colorectal cancer with no recurrent carcinoma. Therefore, our work presents an integrated strategy derived from MOF@COF for remarkably augmenting single MWTT to reduce tumor recurrence.
微波热疗 (MWTT) 由于其非侵入性或微创性以及在组织中的深穿透性，在癌症治疗中显示出巨大的前景。然而，MWTT 后不完全消融和许多促肿瘤血管生成因子（如血管内皮生长因子，VEGF）的表达升高仍然是一个障碍，特别是在一些容易复发和转移的肿瘤中，如结直肠癌。在此，我们提出了一种具有微波（MW）热动力学敏化和肿瘤抗血管生成协同作用的共价有机框架包覆金属有机框架（MOF@COF）纳米胶囊。设计了双金属卟啉（BM）的 MOF 作为 MW 敏化剂，以产生用于微波动力学治疗（MWDT）协同 MWTT 的细胞毒性 O 和热。COF 共价涂覆在 BM 上，以进一步增强这两种敏化特性，并负载阿帕替尼的疏水性抑制剂，以下调 VEGF 的表达，抑制肿瘤复发。此外，所包含的 Bi 和卟啉赋予系统 CT 和荧光成像（FI）能力。体内实验验证了这种联合治疗方法显著抑制了结直肠癌的生长，且无复发性癌。因此，我们的工作提出了一种源自 MOF@COF 的综合策略，可显著增强单一 MWTT 以降低肿瘤复发率。
