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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.

The annual prevalence of gastric cancer has increased in recent years. Curcumin (CUR) has shown great potential in the treatment of gastric cancer; however, its low bioavailability and poor efficacy hinder its widespread clinical application. Additionally, CUR has been found to be excellent photosensitizer in photodynamic therapy. In this study, the Fe-based metal-organic framework (MOF) Fe Tetrakis (4-carboxyphenyl) porphyrin (Fe-TCPP，FT) was used as a photosensitizer and mononuclear agent. The natural anti-tumor active ingredient CUR was loaded as both a chemotherapeutic agent and photosensitizer to form the nanoparticles CUR@FT (CF). Finally, a cell-penetrating peptide (CPP10) was modified on the surface of the nanoparticles to construct a drug delivery system (named CPP10-PEG@CUR@FT, CCF) that could actively target tumor cells while exerting a synergistic therapeutic effect of chemotherapy and photodynamic therapy. This can improve the efficacy of CUR as a chemotherapeutic drug or photosensitizer, and the high drug load and pH sensitivity of FT nanoparticles provide an excellent carrier for the efficient delivery of CUR. The polyethene glycol (PEG)-conjugated CPP10 (PEG-CPP10) coating allows nanoparticles to specifically target gastric cancer cells, significantly improving the absorption of nanoparticles in vivo and in vitro and improving biosafety. We evaluated the thermal stability, drug loading capacity, and safety of FT as a drug delivery vehicle. We also assessed the in vitro photodynamic performance and toxicity of various nanoparticles and the targeting and biocompatibility of CPP10-PEG@CUR@FT. CPP10-PEG@CUR@FT could specifically target tumor cells, and its effect on killing gastric cancer cells (MKN45) under light was much stronger than that of free CUR. Its toxicity and side effects to other organs and tissues are low, offering good biosafety. The experimental results showed that FT and CUR exerted synergistic effects on photodynamic therapy and chemotherapy. In summary, our novel CUR-loaded targeted nano drug delivery system offers significant advantages by combining photodynamic therapy and chemotherapy for tumor treatment. This approach introduces a new concept for integrating chemotherapy, photodynamic therapy and targeted drug delivery, potentially providing a new strategy for the clinical treatment of gastric cancer.

Due to the non-specific distribution of drugs in the body and the low concentration at the tumor site in traditional chemotherapy, there are challenges associated with significant side effects and tumor resistance. Therefore, a drug delivery system (DDS) urgently needs to be developed that can precisely target tumors. Metal-organic frameworks (MOFs) possess advantageous characteristics derived from organic and inorganic materials, including small particle size, large specific surface area, high drug loading capacity, adjustable structure and pore size, as well as ease of modification. Consequently, MOFs offer unique advantages for designing active targeting, passive targeting, and stimulus-responsive targeting strategies and have become a hot topic of current research on tumor-targeted drug delivery systems. This review will elaborate on the application of MOFs in tumor-targeted drug delivery systems from the perspective of different targeting strategies. We hope that this paper can provide assistance for tumor-targeted therapy.

Abstract Background The pathogenic variants responsible for Birt-Hogg-Dubé syndrome (BHDS) in folliculin (FLCN) gene mostly consist of point mutations. Although large intragenic deletions/duplications have been reported in several case reports, the relationship between large intragenic deletions/duplications and phenotype in BHDS remains unclear. Methods We retrospectively identified and reviewed patients with a large intragenic deletion spanning exons 1–3 and analyzed their phenotypic features to compare with those of point mutation carriers in our hospital from January 1, 2017 to August 31, 2022. Results Twenty unique point mutations (including 4 novel mutations) were detected in 62 patients from 45 families (90%). Exons 1–3 deletion were identified in 8 patients from 5 families (10%) that resided in the same region, Feidong County of Anhui Province, China. Breakpoint analysis indicated that all the deletion breakpoints were flanked by Alu repeats. The prevalence of exons 1–3 deletion carriers in Feidong County was 8.1-times higher than that for BHDS in Anhui Province, suggesting a clustered phenomenon of exons 1–3 deletion. Significantly increased risk of pneumothorax was observed in those with exons 1–3 deletion compared with point mutations (91% vs. 58%, p value 0.047). The risk of renal cancer may be higher in those with exons 1–3 deletion than for those with point mutations (18% vs. 4%, p > 0.05). Conclusions Large intragenic deletion of exons 1–3 in FLCN was identified as a local aggregation phenomenon in Feidong County, China, and was associated with a significantly higher risk of pneumothorax compared to those with point mutations.

Polyphyllin I (PPI) is a naturally active steroidal saponin that has good therapeutic effects in various cancers, such as liver and lung cancers. However, owing to its non-selective distribution in various tissues, it is toxic and has side effects on normal human organs while taking effect. To solve this problem, a unique functionalized nanomaterial called metal–organic frameworks (MOFs) was prepared as a targeted nanoparticle for tumor therapy. MOFs are porous coordination polymers that can achieve precise structural and functional adjustability by regulating the organic ligands and metal ions. IRMOF-8 with a multidimensional network topology whose aperture matched the size of PPI was selected to load the PPI. In this study, PPI was loaded into IRMOF-8 via ex situ encapsulation. Drug-loaded nanoparticles (NPs) were coated with polyethylene glycol (PEG) coupled to cell-penetrating peptides (CPPs). The obtained nanoplatform denoted as PEG-CPP44/PPI@IRMOF-8 NPs had a spherical shape, a rough and uneven surface, an average particle size of 202.97 nm, excellent drug loading (33.37%), and showed release behavior. In addition, the NPs showed remarkable targeting selectivity for cellular uptake and in vivo imaging. More importantly, it exhibited good antitumor activity in vivo and in vitro. It not only increased the therapeutic efficiency of PPI for liver cancer but also reduced the damage caused by PPI to normal organs. The preparation of the functional nanoplatform (PEG-CPP44/PPI@IRMOF-8) shows the advantages and highlights of MOF-based drug delivery systems and can help in the follow-up precise treatment of tumors.

Metal–organic frameworks (MOFs) with tunable structures, high porosity, and abundant active sites are considered to be promising drug delivery systems (DDSs). In this study, novel MOFs-based nanoparticles (CUR@IRMOF-16) were successfully prepared using Zn-based IRMOF-16 as a carrier and curcumin (CUR) as the model drug. This nanocargo delivery platform has dual capabilities, enabling simultaneous drug delivery and fluorescence imaging. In vitro release experiments showed that nanoparticles were released more quickly under mildly acidic conditions, which proved their potential for tumor microenvironment-responsive drug release. Through in vitro cell experiments, it was found that the nano-drug platform had high antitumor cytotoxicity, which may be related to the mechanism of increasing intracellular reactive oxygen species (ROS), reducing intracellular mitochondrial membrane potential (MMP), and inducing apoptosis. In addition, confocal laser microscopy showed that CUR@IRMOF-16 could localize to the nucleus to exert an antitumor effect. Meanwhile, CUR@IRMOF-16 exhibited superior antitumor activity compared with pure CUR in vitro experiments. The biocompatibility test of IRMOF-16 showed reasonable biosafety, and no evidence of obvious toxicity was observed in vitro. CUR@IRMOF-16 has unique advantages with regard to pH response, biocompatibility, and antitumor efficacy, indicating that the nano-drug platform is a promising drug delivery carrier with an antitumor effect.

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.

Context Acetylshikonin, a naphthoquinone derivative, is mainly extracted from some species of the family Boraginaceae, such as Lithospermum erythrorhizon Sieb. et Zucc., Arnebia euchroma (Royle) Johnst., and Arnebia guttata Bunge. As a bioactive compound, acetylshikonin has attracted much attention because of its broad pharmacological properties. Objective This review provides a comprehensive summary of the pharmacology, toxicity, and pharmacokinetics of acetylshikonin focussing on its mechanisms on the basis of currently available literature. Methods The information of acetylshikonin from 1977 to 2020 was collected using major databases including Elsevier, Scholar, PubMed, Springer, Web of Science, and CNKI. Acetylshikonin, pharmacology, toxicity, pharmacokinetics, and naphthoquinone derivative were used as key words. Results According to emerging evidence, acetylshikonin exerts a wide spectrum of pharmacological effects such as anticancer, anti-inflammatory, lipid-regulatory, antidiabetic, antibacterial, antifungal, antioxidative, neuroprotective, and antiviral properties. However, only a few studies have reported the adverse effects of acetylshikonin, with respect to reproductive toxicity and genotoxicity. Pharmacokinetic studies demonstrate that acetylshikonin is associated with a wide distribution and poor absorption. Conclusions Although experimental data supports the beneficial effects of this compound, acetylshikonin cannot be considered as a therapy drug without further investigations, especially, on the toxicity and pharmacokinetics.

Ovarian cancer is one of the most lethal gynecological malignancies, because of metastatic dissemination with poor late clinical therapy. Maggots have been used in traditional Chinese medicine, where they are also known as ‘Wu Gu Chong’. Previous studies have indicated that maggot extract (ME) was beneficial for the treatment of gastric cancer when combined with other drugs, but the effect on anti-ovarian cancer and the underlying mechanism remains unclear. The aim of this study was to investigate the effects of ME on suppressing the proliferation and migration of ovarian cancer cells, and to clarify the underlying mechanism. In this research, Cell Counting Kit-8 (CCK-8), colony formation assay, and luciferase-positive cell quantification assay were employed to identify the inhibitory effects of ME on cell proliferation. Then, the pro-apoptosis and anti-metastasis effects of ME were explored by Western blot, dual annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, immunofluorescent staining, and wound-healing assay. We further established a xenograft model by subcutaneously or intraperitoneally injecting BALB/c nude mice with SKOV3 cells stably expressing luciferase, and the mice were treated with ME. The results showed that ME therapy effectively restrained the growth and metastasis of ovarian tumors in vivo. Furthermore, the mRNA levels of cancer factors including heat shock protein 90 alpha family class B member 1 (HSP90AB1), MYC, and insulin like growth factor 1 receptor (IGF1R) were analyzed by quantitative real-time PCR assay to explore the possible antitumor mechanisms of ME. Next, HSP90 ATPase activity was inhibited by geldanamycin in A2780, and the cell viability was shown to be dramatically reduced, decreasing further with the combination of ME and cisplatin. In turn, HSP90AB1 overexpression effectively inhibited the effect of ME in suppressing capability for cell viability and migration. In addition, HSP90AB1 overexpression limited the ability of ME to inhibit expression of MYC and IGF1R, while the opposite effect was observed for expression of pro-apoptosis protein caspase3 and BAX. Therefore, this study confirmed the potential roles and mechanisms of ME in inhibiting the growth and metastasis of ovarian tumors and promoting apoptosis of ovarian cancer cells by inhibiting overexpression of HSP90AB1.

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.

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.

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.

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.

With the rapid development of WLAN, more and more schools and businesses have begun to provide the WLAN for users. However, WLAN is considerably more susceptible to MitM (man- in-the-middle) attack. To overcome it, we propose a dynamic password technology named Two-way Dynamic Authentication Technology (TDAT). It uses two-factor during the initial authentication, and uses a two-way hash chain during the cross-domain authentication. TDAT effectively protects users' authentication credentials and improves users' experience. In an actual wireless network environment, we implement a MitM attack framework based on Rogue AP. Then we effectively prevent this MitM attack by using TDAT. Moreover we analyze the security of TDAT by using BAN logic.

Oridonin (ORI) is a natural active ingredient with strong anticancer activity. But its clinical use is restricted due to its poor water solubility, short half-life, and low bioavailability. The aim of this study is to utilize the metal organic framework material MOF-5 to load ORI in order to improve its release characteristics and bioavailability. Herein, MOF-5 was synthesized by the solvothermal method and direct addition method, and characterized by Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric Analysis (TG), Brunauer−Emmett−Teller (BET), and Dynamic Light Scattering (DLS), respectively. MOF-5 prepared by the optimal synthesis method was selected for drug-loading and in vitro release experiments. HepG2 cells were model cells. MTT assay, 4′,6-diamidino-2-phenylindole (DAPI) staining and Annexin V/PI assay were used to detect the biological safety of blank carriers and the anticancer activity of drug-loaded materials. The results showed that nano-MOF-5 prepared by the direct addition method had complete structure, uniform size and good biocompatibility, and was suitable as an ORI carrier. The drug loading of ORI@MOF-5 was 52.86% ± 0.59%. The sustained release effect was reliable, and the cumulative release rate was about 87% in 60 h. ORI@MOF-5 had significant cytotoxicity (IC50:22.99 μg/mL) and apoptosis effect on HepG2 cells. ORI@MOF-5 is hopeful to become a new anticancer sustained release preparation. MOF-5 has significant potential as a drug carrier material.