Mitigating Doxorubicin‐Induced Cardiotoxicity and Enhancing Anti‐Tumor Efficacy with a Metformin‐Integrated Self‐Assembled Nanomedicine

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Doxorubicin (Dox) is a potent chemotherapeutic agent commonly used in cancer treatment. However, cardiotoxicity severely limited its clinical application. To address this challenge, novel self-assembled nanomedicine platform, PMDDH, developed for the co-delivery of Dox and metformin, an antidiabetic drug with cardioprotective anti-tumor properties. PMDDH integrates metformin into polyethyleneimine-based bioactive excipient (PMet), intercalated double-stranded DNA hyaluronic acid (HA) coating to enhance tumor targeting. The significantly improves pharmacokinetics tumor-targeting capabilities Dox, while enhances drug's activity by downregulating programmed cell death ligand 1 (PD-L1) activating AMP-activated protein kinase (AMPK) signaling pathway. Additionally, component stimulates cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway, which synergizes Dox-induced immunogenic (ICD) promote robust immune response. markedly reduces preserving mitochondrial function, reducing reactive oxygen species (ROS) production, inducing protective autophagy cardiomyocytes. These findings position as promising dual-function that efficacy minimizing systemic toxicity, offering safer more effective alternative therapy.

Language: Английский

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Metformin-mediated protection against doxorubicin-induced cardiotoxicity

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117535 - 117535

Published: Oct. 15, 2024

Language: Английский

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Anti-Diabetic Therapies and Cancer: From Bench to Bedside

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1479 - 1479

Published: Nov. 20, 2024

Diabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention its potential anti-cancer effects, primarily through modulation AMP-activated protein kinase/mammalian target rapamycin (AMPK/mTOR) pathway and induction autophagy. Beyond metformin, other conventional treatments, such as insulin, sulfonylureas (SUs), pioglitazone, dipeptidyl peptidase-4 (DPP-4) inhibitors, have also been examined their roles in biology, though findings are often inconclusive. More recently, novel medications, like glucagon-like peptide-1 (GLP-1) receptor agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) sodium-glucose co-transporter-2 (SGLT-2) revolutionized DM management by not only improving glycemic control but delivering substantial cardiovascular renal benefits. Given diverse metabolic including anti-obesogenic properties, agents now under meticulous investigation influence tumorigenesis advancement. This review aims to offer comprehensive exploration evolving landscape glucose-lowering treatments implications biology. It critically evaluates experimental evidence surrounding molecular mechanisms which medications may modulate oncogenic signaling pathways reshape tumor microenvironment (TME). Furthermore, it assesses translational research clinical trials gauge practical relevance real-world settings. Finally, explores adjuncts treatment, particularly enhancing efficacy chemotherapy, minimizing toxicity, addressing resistance within framework immunotherapy.

Language: Английский

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Vanillic acid attenuates doxorubicin-induced cardiotoxicity by regulating PINK1/Parkin/Mfn2 signaling pathway

Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 123, P. 106595 - 106595

Published: Nov. 26, 2024

Language: Английский

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