School of Chemistry, College of Science, University of Tehran, Tehran 14155-6455, Iran.
Laboratory of Adsorption and Catalysis, Department of Chemistry, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
ACS Appl Mater Interfaces. 2024 Jun 5;16(22):28245-28262. doi: 10.1021/acsami.4c05989. Epub 2024 May 21.
Engineering bulk covalent organic frameworks (COFs) to access specific morphological structures holds paramount significance in boosting their functions in cancer treatment; nevertheless, scant effort has been dedicated to exploring this realm. Herein, silica core-shell templates and multifunctional COF-based reticulated hollow nanospheres (HCOFs) are novelly designed as a versatile nanoplatform to investigate the simultaneous effect of dual-drug chemotherapy and photothermal ablation. Taking advantage of the distinct structural properties of the template, the resulting two-dimensional (2D) HCOF, featuring large internal voids and a peripheral interconnected mesoporous shell, presents intriguing benefits over its bulk counterparts for cancer treatment, including a well-defined morphology, an outstanding drug loading capability (99.6%) attributed to its ultrahigh surface area (2087 m/g), great crystallinity, improved tumor accumulation, and an adjustable drug release profile. After being loaded with hydrophilic doxorubicin with a remarkable loading capacity, the obtained drug-loaded HCOFs were coated with gold nanoparticles (Au NPs) to confer them with three properties, including pore entrance blockage, active-targeting capability, and improved biocompatibility via secondary modification, besides high near infrared (NIR) absorption for efficient photothermal hyperthermia cancer suppression. The resultant structure was functionalized with mono-6-thio-β-cyclodextrin (β-CD) as a second pocket to load docetaxel as the hydrophobic anticancer agent (combination index = 0.33). The dual-drug-loaded HCOF displayed both pH- and near-infrared-responsive on-demand drug release. and evaluations unveiled the prominent synergistic performance of coloaded HCOF in cancer elimination upon NIR light irradiation. This work opens up a new avenue for exciting applications of structurally engineered HCOFs as hydrophobic/hydrophilic drug carriers as well as multimodal treatment agents.
工程块状共价有机框架（COFs）以获得特定的形态结构对于提高它们在癌症治疗中的功能至关重要；然而，在这一领域的探索甚少。本文中，设计了二氧化硅核壳模板和多功能 COF 基交联中空纳米球（HCOFs）作为一种通用的纳米平台，以研究双重药物化疗和光热消融的协同作用。利用模板的独特结构特性，得到的二维（2D）HCOF 具有大的内部空隙和外围互连的介孔壳，与块状 COF 相比，在癌症治疗方面具有显著的优势，包括明确的形态、出色的载药能力（99.6%归因于其超高的表面积（2087 m/g）、良好的结晶度、提高的肿瘤积累和可调节的药物释放特性。在负载具有显著载药能力的亲水性阿霉素后，负载药物的 HCOFs 被金纳米粒子（Au NPs）包覆，通过二次修饰赋予其三种特性，包括孔入口阻塞、主动靶向能力和提高生物相容性，此外还具有高效近红外（NIR）吸收，用于高效光热高温抑制癌症。所得结构通过单 6-硫-β-环糊精（β-CD）官能化，作为第二个口袋来加载多西紫杉醇作为疏水性抗癌剂（组合指数=0.33）。负载双重药物的 HCOF 表现出 pH 和近红外响应的按需药物释放。体外和体内评估揭示了共载 HCOF 在近红外光照射下消除癌症的显著协同作用。这项工作为结构工程化的 HCOF 作为疏水性/亲水性药物载体以及多模式治疗剂的应用开辟了新途径。
