Bioengineering Division, Hacettepe University, Ankara 06800, Turkey.
Graduate School of Science and Engineering, Hacettepe University, Ankara 06800, Turkey.
ACS Appl Bio Mater. 2024 May 20;7(5):2781-2793. doi: 10.1021/acsabm.3c01181. Epub 2024 Feb 21.
A synergistic therapy agent (STA) with photothermal, photodynamic, chemodynamic, and starvation therapy (PTT, PDT, CDT, and ST) functions was developed. Hollow, mesoporous, and nearly uniform CeO nanoparticles (H-CeO NPs) were synthesized using a staged shape templating sol-gel protocol. Chlorin e6 (Ce6) was adsorbed onto H-CeO NPs, and a thin polydopamine (PDA) layer was formed on Ce6-adsorbed H-CeO NPs. Glucose oxidase (GOx) was bound onto PDA-coated Ce6-adsorbed H-CeO NPs to obtain the targeted STA (H-CeO@Ce6@PDA@GOx NPs). A reversible photothermal conversion behavior with the temperature elevations up to 34 °C was observed by NIR laser irradiation at 808 nm. A cascade enzyme system based on immobilized GOx and intrinsic catalase-like activity of H-CeO NPs was rendered on STA for enhancing the effectiveness of PDT by elevation of ROS generation and alleviation of hypoxia in a tumor microenvironment. Glucose-mediated generation of highly toxic hydroxyl radicals (OH) was evaluated for CDT. The effectiveness of PDT on glioblastoma T98G cells was markedly enhanced by O generation started by the decomposition of glucose. A similar increase in cell death was also observed when ST and CDT functions were enhanced by photothermal action. The viability of T98G cells decreased to 10.6% by in vitro synergistic action including ST, CDT, PDT, and PTT without using any antitumor agent.
一种具有光热、光动力、化学动力学和饥饿治疗(PTT、PDT、CDT 和 ST)功能的协同治疗剂(STA)被开发出来。采用阶段模板溶胶-凝胶法合成了具有中空、介孔和近均一结构的 CeO 纳米粒子(H-CeO NPs)。氯乙锭(Ce6)被吸附到 H-CeO NPs 上,在 Ce6 吸附的 H-CeO NPs 上形成了一层薄的聚多巴胺(PDA)层。葡萄糖氧化酶(GOx)结合到 PDA 涂层的 Ce6 吸附的 H-CeO NPs 上,得到了靶向 STA(H-CeO@Ce6@PDA@GOx NPs)。在 808nm 的近红外激光照射下,观察到具有可逆光热转换行为的温度升高可达 34°C。基于固定化 GOx 和 H-CeO NPs 固有类过氧化物酶活性的级联酶系统被用于 STA,通过提高 ROS 的产生和减轻肿瘤微环境中的缺氧来增强 PDT 的效果。评估了 STA 中葡萄糖介导的产生高毒性羟基自由基(OH)的能力,用于 CDT。通过葡萄糖分解引发的 O 的产生,显著增强了 PDT 对神经胶质瘤 T98G 细胞的效果。当通过光热作用增强 ST 和 CDT 功能时,也观察到细胞死亡的类似增加。在没有使用任何抗肿瘤药物的情况下,体外协同作用(包括 ST、CDT、PDT 和 PTT)使 T98G 细胞的存活率降低至 10.6%。
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