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.

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.

Polygonum multiflorum Thunb. (PM), called Heshouwu in China, is a popular Chinese medicine in clinical practice. Several clinical studies have been conducted to evaluate the traditional therapeutic claims and to study the potential therapeutic activity of PM in dyslipidemia and neurodegenerative diseases, highlighting available clinical evidence. In recent years, reports on clinical adverse reactions of Raw Radix P. multiflorum (RPM) and P. multiflorum Praeparata (PMP) have been on the increase, especially with respect to liver injury. Most liver injury cases had been assessed for causality using RUCAM (Roussel Uclaf Causality Assessment Method) in this paper. However, the components of PM responsible for the reported hepatotoxic effects have not yet been identified. Moreover, many of the reports are contradictory, while studies on the mechanism involved in PM-induced liver damage are not comprehensive. This study was aimed at reviewing the status of research on liver injury due to PM, including clinical characteristics, risk factors, material basis research and mechanism of action, with a view to understanding PM-induced hepatotoxicity, and taking reasonable and effective measures to prevent it. In short, quality control is still one of the major safety problems in TCM drug safety concerns. The model of safety monitoring and risk management of PM drugs is not yet developed. Indeed, the characteristics and risk factors associated with PM require both proper understanding and control of the risk by strengthening standardization of clinical applications, basic science research, quality control in manufacturing, active monitoring methodology and enhancement of international communication and cooperation. Measures should also be encouraged and implemented to promote healthy development of the TCM industry.

The antitumor activity of triptolide (TP) has received widespread attention, although its toxicity severely limits its clinical application. Therefore, the design of a targeted drug delivery system (TDDS) has important application prospects in tumor treatment. Metal–organic frameworks (MOFs), with high drug-carrying capacity and good biocompatibility, have aroused widespread interest for drug delivery systems. Herein, folic acid (FA) and 5-carboxylic acid fluorescein (5-FAM) were used to modify Fe-MIL-101 to construct a functionalized nano-platform (5-FAM/FA/TP@Fe-MIL-101) for the targeted delivery of the anti-tumor drug triptolide and realize in vivo fluorescence imaging. Compared with Fe-MIL-101, functionalized nanoparticles not only showed better targeted therapy efficiency, but also reduced the systemic toxicity of triptolide. In addition, the modification of 5-FAM facilitated fluorescence imaging of the tumor site and realized the construction of an integrated nano-platform for fluorescence imaging and treatment. Both in vitro and in vivo studies of functionalized nanoparticles have demonstrated excellent fluorescence imaging and synergistic targeting anticancer activity with negligible systemic toxicity. The development of functional nano-platform provides new ideas for the design of MOF-based multifunctional nano-drug delivery system, which can be used for precise treatment of tumor.

Curcumin (CUR) has a bright future in the treatment of cancer as a natural active ingredient with great potential. However, curcumin has a low solubility, which limits its clinical application. In this study, IRMOF-10 was created by the direct addition of triethylamine, CUR was loaded into IRMOF-10 using the solvent adsorption method, and the two were characterized using a scanning electron microscope (SEM), X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG) methods, and Brunauer–Emmett–Teller (BET) analysis. We also used the MTT method, 4′,6-diamidino-2-phenylindole (DAPI) staining, the annexin V/PI method, cellular uptake, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) to perform a safety analysis and anticancer activity study of IRMOF-10 and CUR@IRMOF-10 on HepG2 cells. Our results showed that CUR@IRMOF-10 had a CUR load of 63.96%, with an obvious slow-release phenomenon. The CUR levels released under different conditions at 60 h were 33.58% (pH 7.4) and 31.86% (pH 5.5). Cell experiments proved that IRMOF-10 was biologically safe and could promote curcumin entering the nucleus, causing a series of reactions, such as an increase in reactive oxygen species and a decrease in the mitochondrial membrane potential, thereby leading to cell apoptosis. In summary, IRMOF-10 is an excellent drug carrier and CUR@IRMOF-10 is an effective anti-liver cancer sustained-release preparation.

The incidence of ocular surface disease (OSD) is increasing, with a trend towards younger ages. However, it is difficult for drugs to reach the deep layers of the cornea due to ocular surface barriers, and bioavailability is less than 5%. In this study, DSPE-PEG2000 was modified with L-valine (L-Val), and an HS15/DSPE-PEG2000-L-Val nanomicelle delivery system containing baicalin (BC) (BC@HS15/DSPE-PEG2000-L-Val) was constructed using thin-film hydration, with a high encapsulation rate, small particle size and no irritation to the ocular surface. Retention experiments on the ocular surface of rabbits and an in vivo corneal permeation test showed that, compared with the control, nanomicelles not only prolonged retention time but also enhanced the ability to deliver drugs to the deep layers of the cornea. The results of a protein inhibition and protein expression assay showed that nanomicelles could increase uptake in human corneal epithelial cells (HCEC) through energy-dependent endocytosis mediated by clathrin, caveolin and the carrier pathway mediated by PepT1 by inhibiting the overexpression of claudin-1 and ZO-1 and suppressing the expression of PepT1-induced by drug stimulation. These results indicate that BC@HS15/DSPE-PEG2000-L-Val is suitable for drug delivery to the deep layers of the ocular surface, providing a potential approach for the development of ocular drug delivery systems.