Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, PO13759, Cairo, Egypt.
Radioactive Isotopes and Generator Department, Hot Labs Center, Egyptian Atomic Energy Authority, PO13759, Cairo, Egypt.
J Mater Chem B. 2024 Jun 27;12(25):6257-6274. doi: 10.1039/d4tb00615a.
Despite enormous advancements in its management, cancer is the world's primary cause of mortality. Therefore, tremendous strides were made to produce intelligent theranostics with mitigated side effects and improved specificity and efficiency. Thus, we developed a pH-sensitive theranostic platform composed of dextran immobilized zinc oxide nanoparticles, loaded with doxorubicin and radiolabeled with the technetium-99m radionuclide (Tc-labelled DOX-loaded ZnO@dextran). The platform measured 11.5 nm in diameter with -12 mV zeta potential, 88% DOX loading efficiency and 98.5% radiolabeling efficiency. It showed DOX release in a pH-responsive manner, releasing 93.1% cumulatively at pH 5 but just 7% at pH 7.4. It showed improved intracellular uptake, which resulted in a high growth suppressive effect against MCF-7 cancer cells as compared to the free DOX. It boasted a 4 times lower IC than DOX, indicating its significant anti-proliferative potential (0.14 and 0.55 μg ml, respectively). The biological evaluation revealed that its molecular mode of anti-proliferative action included downregulating Cdk-2, which provoked G1/S cell cycle arrest, and upregulating both the intracellular ROS level and caspase-3, which induced apoptosis and necrosis. The experiments in Ehrlich-ascites carcinoma bearing mice demonstrated that DOX-loaded ZnO@dextran showed a considerable 4-fold increase in anti-tumor efficacy compared to DOX. Moreover, by utilizing the diagnostic radionuclide (Tc), the radiolabeled platform (Tc-labelled DOX-loaded ZnO@dextran) was monitored in tumor-bearing mice, revealing high tumor accumulation (14% ID g at 1 h p.i.) and reduced uptake in non-target organs with a 17.5 T/NT ratio at 1 h p.i. Hence, Tc-labelled DOX-loaded ZnO@dextran could be recommended as a rectified tumor-targeted theranostic platform.
尽管癌症的治疗取得了巨大进展，但它仍是全球主要的死亡原因。因此，人们做出了巨大的努力来开发具有减轻副作用、提高特异性和效率的智能治疗方法。因此，我们开发了一种由葡聚糖固定的氧化锌纳米粒子组成的 pH 敏感治疗平台，负载多柔比星并放射性标记锝-99m 放射性核素（Tc 标记的 DOX 负载 ZnO@葡聚糖）。该平台的直径为 11.5nm，zeta 电位为-12mV，DOX 负载效率为 88%，放射性标记效率为 98.5%。它在 pH 响应方式下释放 DOX，在 pH 5 时累积释放 93.1%，而在 pH 7.4 时仅释放 7%。它显示出改善的细胞内摄取，与游离 DOX 相比，对 MCF-7 癌细胞的生长抑制作用更高。它的 IC 比 DOX 低 4 倍，表明其具有显著的抗增殖潜力（分别为 0.14 和 0.55μgml）。生物学评价表明，其抗增殖作用的分子模式包括下调 Cdk-2，导致 G1/S 细胞周期停滞，以及上调细胞内 ROS 水平和 caspase-3，诱导细胞凋亡和坏死。在荷 Ehrlich 腹水癌小鼠的实验中，负载 DOX 的 ZnO@葡聚糖的抗肿瘤疗效比 DOX 提高了 4 倍。此外，通过利用诊断放射性核素（Tc），在荷瘤小鼠中监测放射性标记的平台（Tc 标记的 DOX 负载 ZnO@葡聚糖），发现其在肿瘤中的积累很高（1 h p.i.时为 14% ID g），而在非靶器官中的摄取减少，1 h p.i.时的 T/NT 比值为 17.5。因此，Tc 标记的 DOX 负载 ZnO@葡聚糖可作为一种经修正的肿瘤靶向治疗平台。
