Glycopolymer-Functionalized MOF-808 Nanoparticles as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and Floxuridine

Abstract

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.

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“…Also, the authors investigated the relationship between pore size and loading and releasing of the drug. Duman and coworkers [ 39 ] used MOF‐808 functionalized with poly(acrylic acid‐mannose acrylamide) (PAAMAM) glycopolymer NPs for co‐delivery of carboplatin and floxuridine. The MOF was found to induce selective drug delivery and also increased the therapeutic effect of chemotherapy (CT).…”

“…The MOF comprised a 4,4 0 -(diazene-1,2-diyl)bis (3,5-difluorobenzoic acid) ligand (UiO-AZB-F) that responded to green light. 4,4 0 -azobenzenedicarboxylic 57.9 (wt%) [38] UiO-66, UiO-66-NH 2 SiO 2 FA-pluronic F127 DOX -5.6 (wt%) [43] Ni-Ta core-shell MOF FA-CS DOX-CUR 13% increment (pH 5) - [41] MOF-808 PAAMAM Carboplatin/ Floxuridine -- [39] MOF IPI549, CpG Tolllike receptor --4 4 [57] (IRMOF3)-Zn 2+ FA DSF -- [42] Zn-H 2 BDP-X (X = H, NO acid (AZB) possesses a photoswitchable azobenzene ligand. After exposure to light, this compound experienced photoisomerization, which led to the decomposition of the network and the release of the encapsulated cargo.…”

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“…Viruses often use mannose-containing structures to target mannose receptors, type C lectins, so carriers with mannose are most often used for immunotherapy. The mannose-binding lectin receptors CD206 are overexpressed in many cells, including immune cells and liver cancer cells [ 266 ].…”

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“…These issues drive ongoing research that targets new nanosystems for cancer treatment. Forgan et al developed glycopolymer-functionalized MOF-808 nanoparticles for the cancer-targeted codelivery of carboplatin and floxuridine drugs, showing a high cytotoxicity to HepG2 human hepatocellular carcinoma cells . Khashab and co-workers prepared magnetic nanowires coated with biologics-loaded zeolitic imidazolate frameworks and cellular membranes for multimodal cancer therapy .…”