In recent years, metal organic frameworks (MOFs) have been widely developed as vehicles for the effective delivery of drugs to tumor tissues. Due to the high loading capacity and excellent biocompatibility of MOFs, they provide an unprecedented opportunity for the treatment of cancer. However, drugs which are commonly used to treat cancer often cause side effects in normal tissue accumulation. Therefore, the strategy of drug targeting delivery based on MOFs has excellent research significance. Here, we introduce several intelligent targeted drug delivery systems based on MOFs and their characteristics as drug-loading systems, and the challenges of MOFs are discussed. This article covers the following types of MOFs: Isoreticular Metal Organic Frameworks (IRMOFs), Materials of Institute Lavoisier (MILs), Zeolitic Imidazolate Frameworks (ZIFs), University of Oslo (UiOs), and MOFs-based core-shell structures. Generally, MOFs can be reasonably controlled at the nanometer size to effectively achieve passive targeting. In addition, different ligands can be modified on MOFs for active or physicochemical targeting. On the one hand, the targeting strategy can improve the concentration of the drugs at the tumor site to improve the efficacy, on the other hand, it can avoid the release of the drugs in normal tissues to improve safety. Despite the challenges of clinical application of MOFs, MOFs have a number of advantages as a kind of smart delivery vehicle, which offer possibilities for clinical applications.

Metal–organic frameworks (MOFs) are porous materials composed of metal ions and organic ligands. Due to their large surface area, easy modification, and good biocompatibility, MOFs are often used in bio-related fields. Fe-based metal–organic frameworks (Fe-MOFs), as important types of MOF, are favored by biomedical researchers for their advantages, such as low toxicity, good stability, high drug-loading capacity, and flexible structure. Fe-MOFs are diverse and widely used. Many new Fe-MOFs have appeared in recent years, with new modification methods and innovative design ideas, leading to the transformation of Fe-MOFs from single-mode therapy to multi-mode therapy. In this paper, the therapeutic principles, classification, characteristics, preparation methods, surface modification, and applications of Fe-MOFs in recent years are reviewed to understand the development trends and existing problems in Fe-MOFs, with the view to provide new ideas and directions for future research.

Metal organic frameworks (MOFs) are widely used in drug carrier research due to their tunability. The properties of MOFs can be adjusted through incorporation of mono-substituents to obtain pharmaceutical carriers with excellent properties. In this study, different functional groups of –NH₂, –CH₃, –Br, –OH and –CH₂ CH are connected to MOF-5 to analyse the effect of mono-substituent incorporation on drug delivery properties. The resulting MOFs have similar structures, except for Br–MOF. The pore size of this series of MOFs ranges from 1.04 nm to 1.10 nm. Using oridonin (ORI) as a model drug, introduction of the functional groups appears to have a significant effect on the drug delivery performance of the MOFs. The IRMOFs can be ranked according to drug-loading capacity: MOF-5 > HO–MOF-5 > H₃C–MOF-5 = Br–MOF-5 > H₂N–MOF-5 > CH₂ CH–MOF-5. The ORI release from ORI @IRMOFs is explored at two different pH values: 7.4 and 5.5, and the ORI@IRMOFs are ranked according to the cumulative release percentage of ORI: ORI@MOF-5 > ORI@Br–MOF-5 > ORI@H₃C–MOF-5 > ORI@H₂N–MOF-5 > CH₂ CH–MOF-5 > ORI@ HO–MOF-5. In particular, the release behaviour of ORI@MOFs is described through a new model. The different drug delivery performance of MOFs may be due to the complex interactions between MOFs and ORI. In addition, the introduction of single substituents does not change the biocompatibility of MOFs. MTT in vitro experiments prove that this series of MOFs has low cytotoxicity. This study shows that the incorporation of single substituents can effectively adjust the drug delivery behaviour of MOFs, which is conducive to realization of personalized drug delivery modes. The introduction of active groups can also facilitate post-synthesis modification to achieve coupling of targeting groups. MOFs incorporated with single substituents perform favorably in terms of use as biomedical drug delivery alternative carriers in effective drug payload and flexible drug release.

Oxidative damage to retinal pigment epithelial (RPE) has been identified as one of the major regulatory factors in the pathogenesis of age-related macular degeneration (AMD). Catalpol is an iridoid glucoside compound that has been found to possess potential antioxidant activity. In the present study, we aimed to investigate the protective effect of catalpol on RPE cells under oxidative stress and to elucidate the potential molecular mechanism involved. We found that catalpol significantly attenuated hydrogen peroxide (H₂O₂)-induced cytotoxicity, G0/G1 phase cell cycle arrest, and apoptosis in RPE cells. The overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA) stimulated by oxidative stress and the corresponding reductions in antioxidant glutathione (GSH) and superoxide dismutase (SOD) levels were largely reversed by catalpol pretreatment. Moreover, catalpol pretreatment markedly activated the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its downstream antioxidant enzymes, catalase (CAT), heme oxygenase-1 (HO-1), and NADPH dehydrogenase (NQO1). It also increased the expression levels of cyclin E, Bcl-2, cyclin A, and cyclin-dependent kinase 2 (CDK2) and decreased the expression levels of Bax, Fas, cleaved PARP, p-p53, and p21 cleaved caspase-3, 8, and 9. The oxidative stress-induced formation of the Keap1/Nrf2 complex in the cytoplasm was significantly blocked by catalpol pretreatment. These results indicate that catalpol protected RPE cells from oxidative stress through a mechanism involving the activation of the Keap1/Nrf2/ARE pathways and the inactivation of oxidative stress-mediated pathways of apoptosis.

Ferroptosis is a recently discovered pathway for regulated cell death pathway. However, its efficacy is affected by limited iron content and intracellular ion homeostasis. Here, we designed a metal-organic framework (MOF)-based nanoplatform that incorporates calcium peroxide (CaO₂) and oridonin (ORI). This platform can improve the tumor microenvironment and disrupt intracellular iron homeostasis, thereby enhancing ferroptosis therapy. Fused cell membranes (FM) were used to modify nanoparticles (ORI@CaO₂@Fe-TCPP, NPs) to produce FM@ORI@CaO₂@Fe-TCPP (FM@NPs). The encapsulated ORI inhibited the HSPB1/PCBP1/IREB2 and FSP1/COQ10 pathways simultaneously, working in tandem with Fe³⁺ to induce ferroptosis. Photodynamic therapy (PDT) guided by porphyrin (TCPP) significantly enhanced ferroptosis through excessive accumulation of reactive oxygen species (ROS). This self-amplifying strategy promoted robust ferroptosis, which could work synergistically with FM-mediated immunotherapy. In vivo experiments showed that FM@NPs inhibited 91.57% of melanoma cells within six days, a rate 5.6 times higher than chemotherapy alone. FM@NPs were biodegraded and directly eliminated in the urine or faeces without substantial toxicity. Thus, this study demonstrated that combining immunotherapy with efficient ferroptosis induction through nanotechnology is a feasible and promising strategy for melanoma treatment.

In recent years, small interfering RNA (siRNA) has been widely used in the treatment of human diseases, especially tumors, and has shown great appeal. However, the clinical application of siRNA faces several challenges. Insufficient efficacy, poor bioavailability, poor stability, and lack of responsiveness to a single therapy are the main problems affecting tumor therapy. Here, we designed a cell-penetrating peptide (CPP)-modified metal organic framework nanoplatform (named PEG-CPP33@ORI@survivin siRNA@ZIF-90, PEG-CPP33@NPs) for targeted co-delivery of oridonin (ORI), a natural anti-tumor active ingredient) and survivin siRNA in vivo. This can improve the stability and bioavailability of siRNA and the efficacy of siRNA monotherapy. The high drug-loading capacity and pH-sensitive properties of zeolite imidazolides endowed the PEG-CPP33@NPs with lysosomal escape abilities. The Polyethylene glycol (PEG)-conjugated CPP (PEG-CPP33) coating significantly improved the uptake in the PEG-CPP33@NPs in vitro and in vivo. The results showed that the co-delivery of ORI and survivin siRNA greatly enhanced the anti-tumor effect of PEG-CPP33@NPs, demonstrating the synergistic effect between ORI and survivin siRNA. In summary, the novel targeted nanobiological platform loaded with ORI and survivin siRNA presented herein showed great advantages in cancer therapy, and provides an attractive strategy for the synergistic application of chemotherapy and gene therapy.