Atovaquone-Coordinated Copper-Polyphenol Nanoplatform Orchestrates Dual Metabolic Interference for Synergistic Cuproptosis and Apoptosis

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Cuproptosis, a copper-dependent cell death mechanism, is hindered by tumor microenvironment (TME)-driven resistance including glutathione (GSH)-mediated copper detoxification and hypoxia-induced metabolic adaptation. We propose "dual interference" strategy to amplify cuproptosis synergistically targeting iron–sulfur (Fe–S) cluster proteins suppressing oxidative phosphorylation (OXPHOS). A TME-responsive nanoplatform (ACH NPs) was constructed based on copper-shikonin coordination network (CuSK), the OXPHOS inhibitor atovaquone (ATO), hyaluronic acid (HA). Upon GSH/acid-triggered release, Cu+/Cu2+ ATO/SK induced irreversible damage: (1) Copper overload induces dihydrolipoamide transacetylase (DLAT) aggregation Fe–S loss, directly disrupting mitochondrial complexes I–III functions; (2) ATO further suppresses complex III activity, reducing oxygen consumption blocking ATP synthesis exacerbate crisis; (3) Concurrently, Cu+-catalyzed Fenton-like reactions synergize with SK-driven stress generate •OH radicals, activating Caspase-3-dependent apoptosis. In vivo experiments verified that this dual interference effectively inhibited growth (86.8% suppression). These findings not only expand theoretical boundaries of but also establish promising paradigm for cancer therapy through coordinated metal homeostasis vulnerabilities.

Language: Английский

Manganese-Based Nanotherapeutics for Targeted Treatment of Breast Cancer

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Breast cancer (BC) is one of the most common cancers among women and associated with high mortality. Traditional modalities, including surgery, radiotherapy, chemotherapy, have achieved certain advancements but continue to combat challenges harm healthy tissues, resistance treatment, adverse drug reactions. The rapid in nanotechnology recently facilitated exploration innovative strategies for breast therapy. Manganese-based nanotherapeutics attracted great attention because their unique characteristics such as tunable structures/morphologies, versatility, magnetic/optical properties, strong catalytic activities, excellent biodegradability, biocompatibility. In this review, we highlighted different types Mn-based modulate TME, metal-immunotherapy, alleviating tumor hypoxia, increasing reactive oxygen species production, emphasized its role magnetic resonance imaging (MRI)-guided therapy, photoacoustic imaging, theranostic-based therapy along a therapeutic carrier, all which were discussed context cancer. Hopefully, present review will provide insights into current landscape future directions multifunctional applications field treatment.

Language: Английский