Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer Therapy

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

Piezocatalyst-enabled sonopiezoelectric therapy offers noninvasive treatment with high spatiotemporal selectivity, yet existing piezocatalysts are limited by suboptimal efficacy, cancer cell resistance to oxidative stress, and biosafety concerns. Here, hafnia (HfO2), one of the only few FDA-approved inorganic nanomaterials for clinical trials, is identified as a promising piezocatalyst translational potential enzymatic PANoptosis-boosted nanocatalytic therapy. Specifically, engineered transition metal-substituted HfO2 nanocatalysts synthesized optimize piezoelectric enzyme-mimicking activities. Among these, Mn-substituted 20% Mn ratio (HMO) demonstrates superior performance in sono-triggered reactive oxygen species generation, attributed its reduced bandgap increased vacancies. HMO also exhibits multiple activities, including peroxidase (POD), catalase (CAT), glutathione (GPx), amplifying stress through tumor-specific catalytic reactions. These dual effects enable activation PANoptosis elicit robust antitumor immune response. Biological evaluations show significant tumor suppression responses HMO-mediated Unlike utilizing radiosensitization ability clinic, this work unveils distinctive effect multienzymatic activities HfO2-based biomedical applications, holding overcome challenges radiation damage associated radiotherapy.

Язык: Английский

Integrating Proteolysis‐Targeting Chimeras (PROTACs) with Delivery Systems for More Efficient and Precise Targeted Protein Degradation

Macromolecular Rapid Communications, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

Targeted protein degradation (TPD) using the proteolysis-targeting chimeras (PROTACs) is emerging as a revolutionary technology, offering potential strategy for cancer treatment by inducing of overexpressed oncogenic proteins in tumors. PROTACs function recruiting E3 ligases and utilizing ubiquitin-proteasome pathway (UPS) to catalyze target proteins. Compared traditional small molecules inhibitors, exhibit enhanced selectivity, ability overcome drug resistance, traditionally deemed "undruggable". However, poor water solubility low cellular permeability significantly limit their pharmacokinetic properties, while systemic toxicity may hinder clinical application. To address these limitations, strategies that integrate with delivery systems are gaining attention. This review summarizes latest advancements various enhance vivo efficacy reduce off-target effects PROTACs, including prototype nanoparticles, covalent modification-based prodrug strategies, innovative multi-headed designs, microneedle systems, discussing design principles associated challenges. The combination potent multifunctional holds promise accelerating translation improving therapeutic treatment.

Язык: Английский