Demir Duman Fatma, Monaco Alessandra, Foulkes Rachel, Becer C Remzi, Forgan Ross S
WestCHEM, School of Chemistry, University of Glasgow, University Avenue, Glasgow G12 8QQ, U.K.
Department of Chemistry, University of Warwick, CV4 7AL Coventry, U.K.
ACS Appl Nano Mater. 2022 Oct 28;5(10):13862-13873. doi: 10.1021/acsanm.2c01632. Epub 2022 Jun 22.
Codelivery of chemotherapeutics via nanomaterials has attracted much attention over the last decades due to improved drug delivery to tumor tissues, decreased systemic effects, and increased therapeutic efficacies. High porosities, large pore volumes and surface areas, and tunable structures have positioned metal-organic frameworks (MOFs) as promising drug delivery systems (DDSs). In particular, nanoscale Zr-linked MOFs such as MOF-808 offer notable advantages for biomedical applications such as high porosity, good stability, and biocompatibility. In this study, we report efficient dual drug delivery of floxuridine (FUDR) and carboplatin (CARB) loaded in MOF-808 nanoparticles to cancer cells. The nanoparticles were further functionalized by a poly(acrylic acid-mannose acrylamide) (PAAMAM) glycopolymer coating to obtain a highly selective DDS in cancer cells and enhance the therapeutic efficacy of chemotherapy. While MOF-808 was found to enhance the individual therapeutic effects of FUDR and CARB toward cancerous cells, combining FUDR and CARB was seen to cause a synergistic effect, further enhancing the cytotoxicity of the free drugs. Enhancement of CARB loading and therefore cytotoxicity of the CARB-loaded MOFs could be induced through a modified activation protocol, while coating of MOF-808 with the PAAMAM glycopolymer increased the uptake of the nanoparticles in cancer cells used in the study and offered a particularly significant selective drug delivery with high cytotoxicity in HepG2 human hepatocellular carcinoma cells. These results show how the enhancement of cytotoxicity is possible through both nanovector delivery and synergistic treatment, and that MOF-808 is a viable candidate for future drug delivery studies.
在过去几十年中，通过纳米材料进行化疗药物的共递送因其改善了药物向肿瘤组织的递送、降低了全身效应并提高了治疗效果而备受关注。高孔隙率、大孔体积和表面积以及可调节的结构使金属有机框架（MOF）成为有前景的药物递送系统（DDS）。特别是，纳米级锆连接的MOF（如MOF-808）在生物医学应用中具有显著优势，如高孔隙率、良好的稳定性和生物相容性。在本研究中，我们报告了负载在MOF-808纳米颗粒中的氟尿苷（FUDR）和卡铂（CARB）向癌细胞的高效双药递送。通过聚（丙烯酸-甘露糖丙烯酰胺）（PAAMAM）糖聚合物涂层对纳米颗粒进行进一步功能化，以获得癌细胞中高度选择性的DDS，并提高化疗的治疗效果。虽然发现MOF-808可增强FUDR和CARB对癌细胞的个体治疗效果，但联合使用FUDR和CARB会产生协同效应，进一步增强游离药物的细胞毒性。通过改良的活化方案可诱导增加CARB负载量，从而提高负载CARB的MOF的细胞毒性，而用PAAMAM糖聚合物包覆MOF-808可增加本研究中所用癌细胞对纳米颗粒的摄取，并在HepG2人肝癌细胞中提供具有高细胞毒性的特别显著的选择性药物递送。这些结果表明，通过纳米载体递送和协同治疗都有可能增强细胞毒性，并且MOF-808是未来药物递送研究的可行候选物。
