Injectable Hydrogel-Encapsulating Pickering Emulsion for Overcoming Lenvatinib-Resistant Hepatocellular Carcinoma via Cuproptosis Induction and Stemness Inhibition

Polymers, Год журнала: 2024, Номер 16(17), С. 2418 - 2418

Опубликована: Авг. 26, 2024

Lenvatinib resistance (LenR) presents a significant challenge in hepatocellular carcinoma (HCC) treatment, leading to high cancer-related mortality rates globally. Unlike traditional chemotherapy mechanisms, LenR HCC is primarily driven by increased cancer cell stemness. Disulfiram, (DSF), functioning as Cu ionophore, can coordinate with Cu2+ overcome inhibiting stemness and cuproptosis. However, DSF faces challenges due its poor water solubility, while copper ions present issues related systemic toxicity during widespread use. To address this, CuO nanoparticles (NPs) were co-encapsulated form an oil-in-water Pickering emulsion (DSF@CuO), effectively elevating ion concentrations within the tumor microenvironment (TME). DSF@CuO was then combined sodium alginate (SA) DSF@CuO-SA solution, which gelatinizes situ Ca2+ TME Gel, enhancing stability sustaining release. A Gel exhibits enhanced therapeutic efficacy compared conventional administration methods. It induces mitochondrial dysfunction cuproptosis cells downregulating DLAT, LIAS, CDKN2A, upregulating FDX1. Furthermore, it suppresses pathways through activation of JNK/p38 MAPK pathway inhibition NF-κB NOTCH signaling pathways. These findings suggest that Gels are promising strategy for treating HCC. In vivo vitro models demonstrated efficacy. conclusion, this novel approach underscores Gel’s potential HCC, offering clinical challenge.

Язык: Английский

Unite and Conquer: Association of Two G-Quadruplex Aptamers Provides Antiproliferative and Antimigration Activity for Cells from High-Grade Glioma Patients

Pharmaceuticals, Год журнала: 2024, Номер 17(11), С. 1435 - 1435

Опубликована: Окт. 26, 2024

Background: High-grade gliomas remain a virtually incurable form of brain cancer. Current therapies are unable to completely eradicate the tumor, and tumor cells that survive chemotherapy or radiation therapy often become more aggressive resistant further treatment, leading inevitable relapses. While antiproliferative effects new therapeutic molecules typically primary focus research, less attention is given their influence on cell migratory activity, which can play significant role in recurrence. A potential solution may lie synergistic multiple drugs tumor. Objectives: In this study, we investigated effect combined exposure bi-(AID-1-T), an anti-proliferative aptamer, its analog bi-(AID-1-C), activity human GBM cells. Results: We examined various sequences adding bi-(AID-1-T) bi-(AID-1-C) five cultures. Our findings indicate certain significantly reduced ability migrate proliferate. Additionally, expression Nestin, PARP1, L1CAM, Caveolin-1, c-Myc was downregulated survived exposure, suggesting treatment had persistent antitumor these

Язык: Английский