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Cell Death Discovery · 2024 ·Vol. 10 ·期 1 ·1-12 · IF 6.1

Inhibition of lysosomal TRPML1 channel eliminates breast cancer stem cells by triggering ferroptosis

Fan Chunhong,Wu Haotian,Du Xin,Li Canjun,Zeng Wenping,Qu Lili,Cang Chunlei

Cancer stem cells (CSCs) are a sub-population of cells possessing high tumorigenic potential, which contribute to therapeutic resistance, metastasis and recurrence. Eradication of CSCs is widely recognized as a crucial factor in improving patient prognosis, yet the effective targeting of these cells remains a major challenge. Here, we show that the lysosomal cation channel TRPML1 represents a promising target for CSCs. TRPML1 is highly expressed in breast cancer cells and exhibits sensitivity to salinomycin, a drug known to selectively eliminate CSCs. Pharmacological inhibition and genetic depletion of TRPML1 promote ferroptosis in breast CSCs, reduce their stemness, and enhance the sensitivity of breast cancer cells to chemotherapy drug doxorubicin. The inhibition and knockout of TRPML1 also demonstrate significant suppression of tumor formation and growth in the mouse xenograft model. These findings suggest that targeting TRPML1 to eliminate CSCs may be an effective strategy for the treatment of breast cancer.

研究领域: 肿瘤学 · 药理学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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Food Analytical Methods · 2017 ·Vol. 10 ·期 9 ·3042-3051 · IF 2.038

An Enzyme-Linked Immunosorbent Assay to Detect Salinomycin Residues Based on Immunomagnetic Bead Clean-up

Tian Wenhao,Zhang Xiaoxiao,Song Meirong,Jiang Haiyang,Ding Shuangyang,Shen Jianzhong,Li Jiancheng

Polyether antibiotics have been widely used for the treatment and prevention of coccidiosis in chicken farming. In the present study, an efficient, simple and inexpensive competitive indirect enzyme-linked immunosorbent assay (ciELISA) method based on immunomagnetic sample clean up was developed for salinomycin. Monoclonal antibodies were immobilized on the surface of carboxylic acid magnetic beads (2.8 μm in diameter). After a simple extraction, residues in sample extracts were specifically adsorbed and the supernatant removed by magnetic separation. Analytes retained on the beads were then released by elution prior to ciELISA. The limit of detection for salinomycin in chicken muscle and liver was 22 and 18 ng mL −1 , respectively, and the linear quantitative range was 47–653 ng mL −1 . Intra-assay recoveries ranged from 86.00 to 99.32%, and inter-assay recoveries were between 85.68 and 96.34%. The inhibition efficiency and sensitivity of this method was improved compared with traditional hydrophilic-lipophilic balance column clean up ciELISA. Furthermore, the convenience and repeatability of the immunomagnetic cleanup renders the new method of high value for the analysis of drug residues in complex matrices. The test method of schematic diagram

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 兽医学 · 分析化学 · 食品安全
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2018 · IF 3.997

Vitamin E-based redox-sensitive salinomycin prodrug-nanosystem with paclitaxel loaded for cancer targeted and combined chemotherapy

De-Sheng Liang,Jian Liu,Tao-Xing Peng,Hui Peng,Feng Guo,Hai-Jun Zhong

Cancer stem cells (CSCs) can resist conventional chemotherapy to lead to cancer recurrence. For complete eradication of cancers, an effective CSCs therapeutic strategy should be developed to combine with conventional chemotherapy. In this work, a novel vitamin E-based redox-sensitive salinomycin (SAL, an inhibitor for CSCs) prodrug nanoparticles (TS NPs) and hyaluronic acid (HA)-coated TS NPs (HTS NPs) were fabricated to deliver paclitaxel (PTX) for cancer-targeted and combined chemotherapy. Both TS and HTS prodrug NPs had mean diameter of about 200 nm with uniform size distribution, excellent drug loading capacity for PTX, and glutathione-triggered SAL and PTX release profiles. The HTS prodrug NPs had enhanced cellular uptake efficiency over TS NPs due to CD44 receptor-mediated endocytosis, hence exerting stronger potency of SAL upon CSCs-enriched mammospheres formation and G 0 /G 1 cell phase arresting. Cytotoxicity and 3D tumor spheroids assays demonstrated that both TS and HTS prodrug NPs themself can synergize with loaded PTX to maximize the chemotherapeutic effect. Obviously, the latter demonstrated a more potent anticancer efficacy due to improved intracellular drug delivery efficiency. These results suggested that the designed TS prodrug NPs, especially the coated HTS NPs can serve as an effective anti-CSCs strategy for cancer targeted and combination treatments.

研究领域: 药学 · 纳米技术 · 肿瘤学 · 药物递送系统 · 癌症研究
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SEPARATION AND PURIFICATION TECHNOLOGY · 2025 · IF 9

Self-limiting interfacial synthesis of inorganic thin films for high-performance organic solvent nanofiltration in pharmaceutical applications

Xiaoxiang Cheng,Zhe Xu,Xinsheng Luo,Yi Chai,Jiajian Xing,Xinyu Zhang,Jingtao Xu

Inorganic membranes are prime candidates for organic solvent recovery in the pharmaceutical industry due to their excellent solvent resistance, mechanical strength and durability. However, constructing high-performance inorganic separation layers is still the most challenging aspect in the fabrication of inorganic membranes for organic solvent nanofiltration (OSN). Prussian blue analogues (PBAs) exhibit high chemical stability for their rigid cubic framework with strong covalent metal-cyanide coordination bonds. Inspired by the interfacial polymerization (IP) strategy, this study proposes a simple synthesis method for prussian blue analog thin films (PBA TFs) on porous ceramic substrates, using coordination reactions between K 3 [Fe(CN) 6 ] and acetylacetonate (e.g. Cu(acac) 2 , Mn(acac) 3 or Co(acac) 2 ). The Mn-Fe PBA membrane exhibits high solvent permeance (e.g., 176.4 L·m −2 ·h −1 ·bar −1 for ethyl acetate) and demonstrates a molecular weight cut-off ranging from 665 to 760 Da across six tested solvents. To evaluate the industrial potential of Mn-Fe PBA membranes, solvent recovery experiments were conducted in a twin-stage OSN system using seven active pharmaceutical ingredient (API)/solvent systems. In the tylosin/dimethyl sulfoxide system, the Mn-Fe PBA membrane achieved over 80 % total API retention, maintaining stable performance across multiple cycles. The formation process of PBA TFs was analyzed by adjusting monomer diffusion conditions. Furthermore, molecular dynamics simulations elucidated the film formation mechanism. The self-limiting nature of the IP strategy not only inhibits the formation of PBA large crystals, but also induces the self-assembly of PBA nanocrystals along the n-hexane/water interface, resulting in a complete PBA TF. This IP strategy blazes a new trail for fabrication of high-performance inorganic OSN membranes.

研究领域: 材料科学 · 化学工程 · 膜分离技术 · 制药工程
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