RESUMEN
The effective and targeted treatment of resistant cancer cells presents a significant challenge. Targeting cell ferroptosis has shown remarkable efficacy against apoptosis-resistant tumors due to their elevated iron metabolism and oxidative stress levels. However, various obstacles have limited its effectiveness. To overcome these challenges and enhance ferroptosis in cancer cells, we have developed a self-powered photodynamic therapeutic tablet that integrates a ferroptosis inducer (FIN), imidazole ketone erastin (IKE). FINs augment the sensitivity of photodynamic therapy (PDT) by increasing oxidative stress and lipid peroxidation. Furthermore, they utilize the Fenton reaction to supplement oxygen, generating a greater amount of reactive oxygen species (ROS) during PDT. Additionally, PDT facilitates the release of iron ions from the labile iron pool (LIP), accelerating lipid peroxidation and inducing ferroptosis. In vitro and in vivo experiments have demonstrated a more than 85% tumor inhibition rate. This synergistic treatment approach not only addresses the limitations of inadequate penetration and tumor hypoxia associated with PDT but also reduces the required medication dosage. Its high efficiency and specificity towards targeted cells minimize adverse effects, presenting a novel approach to combat clinical resistance in cancer treatment.
Asunto(s)
Ferroptosis , Neoplasias , Humanos , Resultado del Tratamiento , Prótesis e Implantes , HierroRESUMEN
Geniposidic acid (GPA) is a bioactive compound isolated from Gardenia jasminoides Ellis (Rubiaceae) that has long been used to treat arthritis, jaundice, and hypertension. However, the therapeutic effects of GPA against colitis remain underexplored. This study aimed to investigate the effect of GPA on the remission of colitis and the underlying mechanisms. A DSS-induced colitis mouse model was used to evaluate the influence of GPA on the modulation of gut microbiota and intestinal epithelial barrier function. Our results indicated that GPA improved DSS-induced mouse colitis, including loss of body weight, disease activity index (DAI), colon length, and colonic pathological damage. DSS-induced destruction of the intestinal barrier was also significantly repaired by GPA treatment. In addition, the relative levels of pro-inflammatory cytokines, such as IL-1ß and TNF-α, were markedly alleviated by GPA. Furthermore, western blot analysis revealed that GPA downregulated the protein expression of the nuclear transcription factor NF-κB. Finally, we first demonstrated that GPA could alleviate gut microbiota dysbiosis in mice with colitis by bacterial 16S rRNA sequencing. In conclusion, our study demonstrates the therapeutic and protective effects of GPA on IBD and provides novel insights into the prevention of colitis by targeting gut microbiota metabolism using natural products.
Asunto(s)
Colitis , Microbioma Gastrointestinal , Animales , Ratones , ARN Ribosómico 16S/genética , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Colon , Modelos Animales de Enfermedad , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BLRESUMEN
The rapid and accurate monitoring of viral genes plays an important role in the area of disease diagnosis, biomedical research, and food safety. Herein, we successfully designed a sensing system that combined the technologies of target DNA recycling amplification, magnetic separation, and in situ formation of fluorescent copper nanoclusters (CuNCs) for viral DNA analysis. In the presence of target viral DNA (tDNA), a large quantity of output DNA (oDNA) was produced from hairpin DNA (hDNA) through an exonuclease III-assisted target recycling amplification strategy. Magnetic beads (MBs) labeled with capture DNA (cDNA) were hybridized with oDNA, and the partially complementary oDNA served as a bridge that could link AT-rich dsDNA on the surface of MBs, which led to a decrease of AT-rich dsDNA in solution after magnetic separation. On account of the lack of AT-rich dsDNA as a template in solution, in situ formation of fluorescent CuNCs was blocked, which resulted in a decrease in the fluorescence intensity at 590 nm. Therefore, taking advantage of one-step magnetic separation and in situ formation of CuNCs, the target viral DNA was sensitively and specifically detected in a linear range from 5 pM to 5 nM with a detection limit of 1 pM. The MB-based platform was not only reusable but also achieved magnetic separation, which could eliminate interferences in complex samples. The assay combining the MB-based probe with fluorescent CuNCs provided a universal, label-free, and reusable platform for viral DNA detection.
Asunto(s)
Cobre , ADN Viral , ADN Viral/genética , Genes Virales , Fenómenos Magnéticos , Técnicas de Amplificación de Ácido NucleicoRESUMEN
Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), has attracted great attention because it can effectively inhibit the proliferation and propagation of cancer cells. Recently, heterojunction nanomaterials have shown tremendous application value in the field of biological medicine. In this work, the CeVO4/Au heterojunction nanocrystals (NCs) are designed for photothermal/photoacoustic bimodal imaging-guided phototherapy. The as-synthesized hydrophobic oleic acid (OA)-stabilized CeVO4 nanosheets were modified with HS-PEG-OH for translating into hydrophilic ones, which can significantly improve their stability and biocompatibility. Subsequently, the plasmonic Au nanoparticles were in situ successfully deposited on the surface of HS-PEG-coated CeVO4 to form CeVO4/Au heterojunction NCs for improving the visible and near-infrared light absorption, which results in enhanced photothermal conversion performance and reactive oxygen species (ROS) generation capacity. Thus, the CeVO4/Au can cause more severe damage to cancer cells than pure CeVO4 under NIR laser irradiation. Also, CeVO4/Au can provide distinct tumor contrast by photothermal/photoacoustic bimodal bioimaging. Our results demonstrate that CeVO4/Au NCs could be used as an effective theranostic anticancer agent for near-infrared (NIR) light-mediated PTT and PDT.