Using low - molecular - weight ligands for targeting in integrated chemodynamic/starvation therapy and chemotherapy for prostate cancer

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Targeted therapy enhances tumor elimination while reducing adverse effects by integrating multiple tumoricidal mechanisms. Low molecular weight (LMW) ligands, offering faster pharmacokinetics and improved permeability, present a viable alternative to antibodies. This study presents novel nanomedicine for prostate cancer therapy, leveraging mesoporous silica nanoparticles (MSN) as the nanocarrier encapsulate manganese dioxide (MnO₂) doxorubicin (DOX). The resultant are further coated with polydopamine (PDA) layer covalently conjugated glucose oxidase (GOx), forming MSN@Mn@PDA-GOx/DOX hybrid system (hereafter termed SMPG/DOX NPs). LMW ligands (small molecule inhibitor DCL nanobody VHH) targeting prostate-specific membrane antigen (PSMA) were create DCL-SMPG/DOX VHH-SMPG/DOX. Mn²⁺-mediated Fenton-like reactions converted H₂O₂ into toxic hydroxyl radicals (·OH) under acidic conditions, enabling chemodynamic (CDT). GOx-generated gluconic acid disrupted nutrient supply, inducing starvation (ST). increased acidity amplified reaction, creating "ROS storm" that synergistically enhanced chemotherapy. specificity, efficacy, reduced side effects. In vitro, showed superior cell internalization cytotoxicity compared cellular rates of VHH-SMPG/DOX 34.1% 44.5%, respectively, significantly higher than free DOX uptake (10.3%). Moreover, DCL-SMPG/DOX-induced stronger In vivo studies demonstrated strong anti-tumor activity nanomedicine, underscoring its potential treatment. Further research is needed elucidate antitumor

Language: Английский

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Ultrasound-responsive nanobubble-mediated sonodynamic therapy sensitizes disulfidptosis in the treatment of liver hepatocellular carcinoma

Ultrasonics Sonochemistry, Journal Year: 2025, Volume and Issue: 118, P. 107368 - 107368

Published: April 23, 2025

Disulfidptosis, a newly identified regulated cell death, is linked to tumor progression, particularly in cancers with elevated SLC7A11 expression. This study investigates expression liver hepatocellular carcinoma (LIHC) and evaluates the therapeutic potential of ICG@C3F8-KL nanobubbles (NBs) combined sonodynamic therapy (SDT) for inducing disulfidptosis. Bioinformatics analysis TCGA datasets revealed upregulation LIHC tissues. The synthesized NBs exhibited mean diameter 156.46 nm stable properties, high encapsulation efficiencies 51.32 % ± 0.7 KL 80.15 0.21 ICG. In vitro, NBs, under ultrasound, generated reactive oxygen species (ROS), enhancing cytotoxicity HepG2 cells an IC50 lower than alone. These also inhibited migration colony formation, suggesting disulfidptosis induction via altered glucose uptake NADP+/NADPH ratio, as well F-actin contraction. vivo, accumulated tissues suppressed growth without significant toxicity. Unsupervised clustering disulfidptosis-related genes cohort subtypes distinct prognoses, predictive model based on five key was developed. conclusion, effectively induce disulfidptosis, offering promising strategy treatment, personalized informed by disulfide-associated gene signatures.

Language: Английский

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Cobalt(III) prodrug-based nanomedicine for inducing immunogenic cell death and enhancing chemo-immunotherapy

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 373, P. 493 - 506

Published: July 26, 2024

Language: Английский

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Unveiling disulfidptosis-related biomarkers and predicting drugs in Alzheimer’s disease

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 30, 2024

Alzheimer's disease is the predominant form of dementia, and disulfidptosis latest reported mode cell death that impacts various processes. This study used bioinformatics to analyze genes associated with in comprehensively. Based on public datasets, differentially expressed were identified, immune infiltration was investigated through correlation analysis. Subsequently, hub determined by a randomforest model. A prediction model constructed using logistic regression. In addition, drug-target affinity predicted graph neural network model, results validated molecular docking. Five (PPEF1, NEUROD6, VIP, NUPR1, GEM) identified. The gene set showed significant enrichment for AD-related pathways. regression demonstrated an AUC 0.952, values 0.916 0.864 datasets. analysis revealed heterogeneity between control groups. High-affinity drugs Through our study, potential biomarkers, targeting predicted. These contribute further understanding mechanisms underlying disease.

Language: Английский

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Advanced Biomaterials Derived from Functional Polyphosphoesters: Synthesis, Properties, and Biomedical Applications

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Polyphosphoesters (PPEs) represent an innovative class of biodegradable polymers, with the phosphate ester serving as core repeating unit their polymeric backbone. Recently, biomaterials derived from functionalized PPEs have garnered significant interest in biomedical applications because commendable biocompatibility, biodegradability, and capacity for functional modification. This review commences a brief overview synthesis methodologies distinctive properties PPEs, including thermoresponsiveness, degradability, stealth effect, biocompatibility. Subsequently, delves into latest PPEs-based nanocarriers drug or gene delivery prodrugs scaffolds field, presenting several illustrative examples each application. By encapsulating advancements recent years, this aims to offer enhanced understanding serve reference PPEs.

Language: Английский

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