Nanoarchitectonics with Zinc-Doped Carbon Dots for Mitochondria-Targeted Repair and Regeneration Signaling Amplification in CLI Therapy

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

Published: May 16, 2025

Critical limb ischemia (CLI) faces high rates of amputation and mortality. Despite advancements in surgical endovascular interventions, their invasiveness restricted applicability leave many CLI patients classified as "no-option" cases. Therapeutic angiogenesis strategies offer prospects for revascularization, but efficacy remains suboptimal. Herein, we developed a nanomedicine, mitochondria-targeted zinc-doped ascorbic acid-derived carbon dots (TPP-Zn@ACDs), which simultaneously restores mitochondrial function amplifies regenerative signaling to synergistically boost ischemic limbs. TPP-Zn@ACDs integrate potent antioxidative properties the pro-regenerative effects Zn2+, with triphenylphosphine (TPP) polyethylene glycol (PEG) functionalization endowing precise targeting enhanced biocompatibility, thereby localizing therapeutic core oxidative stress mitigation transduction. In vitro, improved by reducing reactive oxygen species, restoring membrane potential enhancing ATP production, through activation SIRT1/PGC-1α pathway. Further, proliferation, migration, tube formation activities endothelial cells were increased, while hypoxia-induced apoptosis necrosis was inhibited effectively. Notably, leveraging restoration cells, subsequently reprogrammed macrophages from an M1 pro-inflammatory phenotype M2 anti-inflammatory phenotype. vivo, demonstrated remarkable mouse model, achieving robust blood flow recovery, increased microvascular density, immune microenvironment. Together, this study proposes versatile engineering nanomedicine therapy, providing scalable approach breakthrough angiogenic diseases.

Language: Английский

Ferroptosis Inhibition Combats Metabolic Derangements and Improves Cardiac Function in Pulmonary Artery Banded Pigs

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 26, 2024

Abstract Right heart failure (RHF) is a leading cause of mortality in multiple cardiovascular diseases and preclinical human data suggest impaired metabolism significant contributor to right-sided cardiac dysfunction. Ferroptosis nonapopotic form cell death driven by metabolism. Rodent suggests ferroptosis inhibition can restore mitochondrial electron transport chain function enhance contractility left models, but the effects translational large animal models RHF are unknown. Here, we showed ferrostatin-1 mediated antagonism improve right structure pulmonary artery banded pigs. Molecularly, restored cristae combatted downregulation proteins. Metabolomics lipidomics analyses revealed improved fatty acid Thus, these may be therapeutic target for RHF. Graphical

Language: Английский