Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Int J Pharm. 2024 Nov 15;665:124665. doi: 10.1016/j.ijpharm.2024.124665. Epub 2024 Sep 3.
Stimuli-responsive nanoplatforms have been popular in controlled drug delivery research because of their ability to differentiate the tumor microenvironment from the normal tissue environment in a spatiotemporally controllable manner. The synergistic therapeutic approach of combining cancer chemotherapy with photothermal tumor ablation has improved the therapeutic efficacy of cancer therapeutics. In this study, a UiO-66 metal organic framework (MOF)-based system loaded with doxorubicin (DOX), surface decorated with the photothermal agents indocyanine green (ICG) and polydopamine (PDA), and conjugated with transferrin (TF) was successfully designed to operate as a responsive system to pH changes, featuring photothermal capabilities and target specificity for the purpose of treating breast cancer. The synthesized nanoplatform benefits from its uniform size, excellent DOX encapsulation efficiency (91.66 %), and efficient pH/NIR-mediated controlled release of the drug. In vitro photothermal studies indicate excellent photothermal stability of the formulation even after 6 on-off cycles of NIR irradiation. The in vitro cytotoxicity assessment using an NIR laser (808 nm) revealed that the DOX-loaded functionalized UiO-66 nanocarriers had outstanding inhibitory effects on 4T1 cells because of synergistic chemo-photo therapies, with no substantial toxicity by the carriers. In addition, cellular uptake evaluations revealed that UiO-DOX-ICG@PDA-TF could specifically target 4T1 cells on the basis of receptor-mediated internalization of transferrin receptors. Additionally, in vivo toxicity studies in Wistar rats indicated no signs of significant toxicity. The UiO-based nanoformulations effectively inhibited and destroyed cancer cells under 808 nm laser irradiation because of their minimal toxicity, strong biocompatibility, and outstanding synergistic chemo/photothermal/photodynamic treatment.
刺激响应型纳米平台因其能够时空可控地将肿瘤微环境与正常组织环境区分开来，而在控制药物输送研究中受到广泛关注。将癌症化学疗法与光热肿瘤消融相结合的协同治疗方法提高了癌症治疗的疗效。在这项研究中，成功设计了一种基于 UiO-66 金属有机骨架（MOF）的系统，该系统负载多柔比星（DOX），表面修饰光热剂吲哚菁绿（ICG）和聚多巴胺（PDA），并与转铁蛋白（TF）缀合，作为响应系统来操作以应对 pH 值变化，具有光热能力和针对乳腺癌的靶向特异性。合成的纳米平台受益于其均匀的尺寸、出色的 DOX 包封效率（91.66%）以及在 pH/NIR 介导下高效控制药物释放。体外光热研究表明，即使经过 6 次 NIR 照射的开/关循环，该制剂仍具有出色的光热稳定性。使用 NIR 激光（808nm）进行的体外细胞毒性评估表明，负载 DOX 的功能化 UiO-66 纳米载体由于协同的化学-光疗具有出色的抑制 4T1 细胞的作用，而载体本身没有明显的毒性。此外，细胞摄取评估表明，UiO-DOX-ICG@PDA-TF 可以基于转铁蛋白受体的受体介导内化来特异性靶向 4T1 细胞。此外，在 Wistar 大鼠中的体内毒性研究表明没有明显毒性的迹象。基于 UiO 的纳米制剂在 808nm 激光照射下有效抑制和破坏癌细胞，因为它们具有最小的毒性、强大的生物相容性和出色的协同化学/光热/光动力治疗效果。
