College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London WC1N 1AX, UK.
J Colloid Interface Sci. 2023 Dec;651:76-92. doi: 10.1016/j.jcis.2023.07.146. Epub 2023 Jul 25.
One of the major challenges in effective cancer therapy arises because of the hypoxic microenvironment in the tumor. This compromises the efficacy of both chemo- and radiotherapy, and thus hinders patient outcomes. To solve this problem, we constructed polydopamine (PDA)-cloaked Fe-based metal organic frameworks (MOFs) loaded with d-arginine (d-Arg), glucose oxidase (GOX), and the chemotherapeutic drug tirapazamine (TPZ). These offer simultaneous multifaceted therapy combining chemodynamic therapy (CDT)/radiotherapy (RT)/starvation therapy (ST)/gas therapy (GT) and chemotherapy. The particles further can act as contrast agents in magnetic resonance imaging. GOX catalyses the conversion of endogenous glucose and O to hydrogen peroxide and gluconic acid, blocking the cells' energy supply and providing ST. With the resultant acidification of the local environment, the breakdown of the MOF releases TPZ (for chemotherapy) and Fe, which reacts with HO to produce reactive oxygen species and thus stimulates the conversion of d-Arg to NO for GT and RT sensitization. The PDA coating not only seals the pores and chelates Fe to enhance the T-weighted magnetic resonance imaging (MRI) properties, but also is used to graft folate bovine serum albumin (FA-BSA) and thereby target the tumor site. The combined administration of low doses of X-ray irradiation and nanoparticles reduces the side effects on healthy tissue and can prevent lung metastases in mice. This work highlights the synergistic treatment of osteosarcoma via ST/GT/CDT/RT/MRI/ chemotherapy using a PDA-cloaked MOF system.
在有效的癌症治疗中，一个主要的挑战是由于肿瘤中的缺氧微环境。这会降低化疗和放疗的疗效，从而影响患者的治疗效果。为了解决这个问题，我们构建了聚多巴胺（PDA）包裹的负载 d-精氨酸（d-Arg）、葡萄糖氧化酶（GOX）和化疗药物替拉扎胺（TPZ）的基于铁的金属有机骨架（MOFs）。这些提供了联合化学动力学治疗（CDT）/放射治疗（RT）/饥饿治疗（ST）/气体治疗（GT）和化疗的多方面治疗。这些粒子还可以作为磁共振成像的对比剂。GOX 催化内源性葡萄糖和 O2 转化为过氧化氢和葡萄糖酸，阻断细胞的能量供应并提供 ST。随着局部环境的酸化，MOF 的分解释放 TPZ（用于化疗）和 Fe，Fe 与 HO 反应生成活性氧，从而刺激 d-Arg 转化为 NO 以进行 GT 和 RT 敏化。PDA 涂层不仅可以密封孔并螯合 Fe 以增强 T 加权磁共振成像（MRI）特性，还可以用于接枝叶酸牛血清白蛋白（FA-BSA），从而靶向肿瘤部位。联合使用低剂量的 X 射线照射和纳米粒子可以减少对健康组织的副作用，并可以预防小鼠的肺转移。这项工作强调了通过 ST/GT/CDT/RT/MRI/化疗联合使用 PDA 包裹的 MOF 系统协同治疗骨肉瘤。
