Combination of disulfiram and Copper-Cysteamine nanoparticles induces mitochondria damage and promotes apoptosis in endometrial cancer.

Endometrial cancer (EC) stands as one of the most prevalent gynecological malignancies affecting women, with its incidence and disease-related mortality steadily on the rise. Disulfiram (DSF), an FDA-approved medication primarily used for treating alcohol addiction, has exhibited promising anti-tumor properties. Studies have revealed DSF's capacity for enhanced anti-tumor activity, particularly when combined with copper. The novel Copper-Cysteamine (CuCy) compound, Cu3Cl(SR)2 (R[bond, double bond]CH2CH2NH2), showcases photodynamic effects and demonstrates significant anti-tumor potential under various conditions, including exposure to ultraviolet light, X-ray, microwave, and ultrasound. This study delves into exploring the synergistic anti-tumor effects and underlying mechanisms by utilizing copper-cysteamine in conjunction with DSF against endometrial cancer. The investigation involved comprehensive analyses encompassing in vitro experiments utilizing Ishikawa cells, in vivo studies, and transcriptomic analyses. Remarkably, the combined administration of both compounds at a low dose of 0.5 µM exhibited pronounced efficacy in impeding tumor growth, inhibiting blood vessel formation, and stimulating cell apoptosis. Notably, experiments involving transplanted tumors in nude mice vividly demonstrated the significant in vivo anti-tumor effects of this combination treatment. Detailed examination through transmission electron microscopy unveiled compelling evidence of mitochondrial damage, cellular swelling, and rupture, indicative of apoptotic changes in morphology due to the combined treatment. Moreover, transcriptomic analysis unveiled substantial downregulation of mitochondrial-related genes at the molecular level, coupled with a significant hindrance in the DNA repair pathway. These findings strongly suggest that the combined application of CuCy and DSF induces mitochondrial impairment in Ishikawa cells, thereby fostering apoptosis and ultimately yielding potent anti-tumor effects.

Copper-cysteamine nanoparticle-mediated microwave dynamic therapy improves cancer treatment with induction of ferroptosis.

Photodynamic Therapy (PDT) holds a great promise for cancer patients, however, due to the hypoxic characteristics of most solid tumors and the limited penetration depth of light in tissues, the extensive clinical application of PDT is limited. Herein, we report microwave induced copper-cysteamine (Cu-Cy) nanoparticles-based PDT as a promising cancer treatment to overcome cancer resistance in combination with ferroptosis. The treatment efficiency of Cu-Cy-mediated microwave dynamic therapy (MWDT) tested on HCT15 colorectal cancer (CRC) cells via cell titer-blue cell viability assay and live/dead assay reveal that Cu-Cy upon MW irradiation can effectively destroy HCT15 CRC cells with average IC-50 values of 20 µg/mL. The cytotoxicity of Cu-Cy to tumor cells after MW stimulation can be alleviated by ferroptosis inhibitor. Furthermore, Cu-Cy mediated MWDT could deplete glutathione peroxide 4 (GPX4) and enhance lipid peroxides (LPO) and malondialdehyde (MDA). Our findings demonstrate that MW-activated Cu-Cy killed CRC cells by inducing ferroptosis. The superior in vivo antitumor efficacy of the Cu-Cy was corroborated by a HCT15 tumor-bearing mice model. Immunohistochemical experiments showed that the GPX4 expression level in Cu-Cy + MW group was significantly lower than that in other groups. Overall, these findings demonstrate that Cu-Cy nanoparticles have a safe and promising clinical application prospect in MWDT for deep-seated tumors and effectively inhibit tumor cell proliferation by inducing ferroptosis, which provides a potential solution for cancer resistance.

The exploration of quantum dot-molecular beacon based MoS2 fluorescence probing for myeloma-related Mirnas detection.

Highly sensitive and reliable detection of multiple myeloma remains a major challenge in liquid biopsy. Herein, for the first time, quantum dot-molecular beacon (QD-MB) functionalized MoS2 (QD-MB @MoS2) fluorescent probes were designed for the dual detection of multiple myeloma (MM)-related miRNA-155 and miRNA-150. The results indicate that the two probes can effectively detect miRNA-155 and miRNA-150 simultaneously with satisfactory recovery rates, and the limit of detections (LODs) of miRNA-155 and miRNA-150 in human serum are low to 7.19 fM and 5.84 fM, respectively. These results indicate that our method is the most sensitive detection so far reported and that the designed fluorescent probes with signal amplification strategies can achieve highly sensitive detection of MM-related miRNAs for MM diagnosis.

Colorectal liver metastasis: molecular mechanism and interventional therapy.

Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors with a high morbidity additionally, CRC patients may develop liver metastasis, which is the major cause of death. Despite significant advances in diagnostic and therapeutic techniques, the survival rate of colorectal liver metastasis (CRLM) patients remains very low. CRLM, as a complex cascade reaction process involving multiple factors and procedures, has complex and diverse molecular mechanisms. In this review, we summarize the mechanisms/pathophysiology, diagnosis, treatment of CRLM. We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM, further improving the prognosis of CRLM patients.

Aggregation-induced emission luminogens for highly effective microwave dynamic therapy.

Aggregation-induced emission luminogens (AIEgens) exhibit efficient cytotoxic reactive oxygen species (ROS) generation capability and unique light-up features in the aggregated state, which have been well explored in image-guided photodynamic therapy (PDT). However, the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications. Coincidentally, microwaves (MWs) show a distinct advantage for deeper penetration depth in tissues than light. Herein, for the first time, we report AIEgen-mediated microwave dynamic therapy (MWDT) for cancer treatment. We found that two AIEgens (TPEPy-I and TPEPy-PF6) served as a new type of microwave (MW) sensitizers to produce ROS, including singlet oxygen (1O2), resulting in efficient destructions of cancer cells. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22 µM, respectively. Overall, the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT, but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome, thus reducing the occurrence of side-effects of MW radiation.

Study of copper-cysteamine based X-ray induced photodynamic therapy and its effects on cancer cell proliferation and migration in a clinical mimic setting.

Copper-cysteamine as a new generation of sensitizers can be activated by light, X-rays, microwaves, or ultrasound to produce reactive oxygen species. X-ray induced photodynamic therapy (X-PDT) has been studied extensively; however, most of the studies reported so far were conducted in the laboratory, which is not conducive to the clinical translation conditions. In this contribution, for the first time, we investigated the treatment efficiency of copper-cysteamine (Cu-Cy) based X-PDT by mimicking the clinical conditions with a clinical linear accelerator and building deep-seated tumor models to study not only the effectiveness but also its effects on the cell migration and proliferation in the level of the cell, tissue, and animal. The results showed that, without X-ray irradiation, Cu-Cy nanoparticles (NPs) had a low toxicity in HepG2, SK-HEP-1, Li-7, and 4T1 cells at a concentration below 100 mg/L. Interestingly, for the first time, it was observed that Cu-Cy mediated X-PDT can inhibit the proliferation and migration of these cell lines in a dose-dependent manner. Antigen markers of migration and cell proliferation, proliferating cell nuclear antigen (PCNA) and E-cadherin, from tumor tissue in the X-PDT group were remarkably different from that of the control group. Furthermore, the MRI assessment showed that the Cu-Cy based X-PDT inhibited the growth of deeply located tumors in mice and rabbits (p < 0.05) without any obvious toxicities in vivo. Overall, these new findings demonstrate that Cu-Cy NPs have a safe and promising clinical application prospect in X-PDT to improve the efficiency of radiotherapy (RT) for deep-seated tumors and effectively inhibit tumor cell proliferation and migration.

A Photothermal Therapy Strategy for Monitoring Real-Time Temperature in Kidney Cancers by Injecting Gold Nanorods with Phosphors.

Photothermal ablation therapy (PTA) has been widely reported; however, it is not possible to predict the internal temperature of the tumor in real time that causes ineffective treatment and normal tissue burns. Here, we have designed a photothermal therapy strategy under real-time temperature monitoring by injecting gold nanorods (AuNRs) and NaYF4: Yb3+ /Er3+ into the tumor site where AuNRs are used for PTA of cancer cells by converting the absorbed energy into heat and using Yb3+ , Er3+-NaYF 4 phosphors to monitor the temperature inside the tumor. Our experiments confirm the effectiveness of this strategy, which is expected to be an aid in the development of real-time temperature monitoring and effective photothermal therapy for the treatment of cancers.

FeS2 Loaded Porous SiO2 Ball as a Tweezers Recoverable Heterogeneous Fenton Catalyst with Enhanced Recyclability.

We report a novel FeS2 loaded large SiO2 sphere (diameter of 3 cm) via double immobilization with (3-mercaptopropyl)trimethoxysilane (KH590) as a highly efficient, stable, and tweezers-recoverable heterogeneous Fenton-like catalyst (FeS2/KH590/SiO2@KH590). Notably, as-prepared composite catalyst exhibits a significant recycling improvement (10 runs) over free FeS2 powder (3 runs). The outstanding recyclability and stability of FeS2/KH590/SiO2@KH590 can be attributed to the passivation of FeS2 nanoparticles on SiO2 surface by KH590 and subsequent prevention of Fe2+ leaching. Overall, our work provides a new avenue towards fabricating composite Fenton-like catalyst with high stability, enhanced recyclability and the advantage of easy separation.

Single source precursor synthesized CuS nanoparticles for NIR phototherapy of cancer and photodegradation of organic carcinogen.

Herein, we report cost effective and body compatible CuS nanoparticles (NPs) derived from a single source precursor as photothermal agent for healing deep cancer and photocatalytic remediation of organic carcinogens. These NPs efficiently kill MCF7 cells (both in vivo and in vitro) under NIR irradiation by raising the temperature of tumor cells. Such materials can be used for the treatment of deep cancer as they can produce a heating effect using high wavelength and deeply penetrating NIR radiation. Furthermore, CuS NPs under solar light irradiation efficiently convert p-nitrophenol (PNP), an environmental carcinogen, to p-aminophenol (PAP) of pharmaceutical implication. In a nutshell, CuS can be used for the treatment of deep cancer and for the remediation of carcinogenic pollutants. There seems an intrinsic connection between the two functions of CuS NPs that need to be explored in length.

A powerful combination of copper-cysteamine nanoparticles with potassium iodide for bacterial destruction.

Herein, for the first time, we demonstrate that the combination of copper-cysteamine (Cu-Cy) nanoparticles (NPs) and potassium iodide (KI) can significantly inactivate both Gram-positive MRSA and Gram-negative E. coli. To uncover the mystery of the killing, the interaction of KI with Cu-Cy NPs was investigated systematically and the products from their interaction were identified. No copper ions were released after adding KI to Cu-Cy NPs in cell-free medium and, therefore, it is reasonable to conclude that the Fenton reaction induced by copper ions is not responsible for the bacterial killing. Based on the observations, we propose that the major killing mechanism involves the generation of toxic species, such as hydrogen peroxide, triiodide ions, iodide ions, singlet oxygen, and iodine molecules. Overall, the powerful combination of Cu-Cy NPs and KI has good potential as an independent treatment or a complementary antibiotic treatment to infectious diseases.

Two D-π-A Schiff-Base-Functionalized Silica Gel Adsorbents for Preconcentration of Copper Ions in Foods and Water for Detection.

Copper is an essential element in many biological processes and plays an important role in carbohydrate and lipid metabolism. Excess or deficiency of Cu ions can cause disturbances in cellular homeostasis and damage the central nervous system. Here, for the first time, two functionalized silica gel (SG-A and SG-B) adsorbents were prepared and tested for copper detection via the reactions of chlorinated silica gel with two novel D-π-A Schiff base compounds: 2-amino-3-(quinolin-2-ylmethyleneamino)maleonitrile (A) and 2-(4-(diethylamino)-2-hydroxybenzylideneamino)-3-aminomaleonitrile (B) in the thionyl chloride solution, respectively. SG-A and SG-B as adsorbents filled in a microcolumn were used to enrich trace Cu ions in foods and water with the detection of flame atomic absorption spectrometry. Because of the strong coordination between two D-π-A Schiff base compounds and Cu2+ ions, the stable heterocyclic Cu2+-SG-A/B complex is formed. For a sample volume of 30 mL, detection limits of 0.09 µg L-1 and 0.15 µg L-1 have been achieved. The results of selectivity study show that the two adsorbents can selectively extract Cu2+ in complex matrixes with other metal cations. The methods have been successfully applied to the determination of Cu2+ content in various real samples, and the detection sensitivity that we report here is better than most results reported using modified silica gels.