Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Mitigating Doxorubicin‐Induced Cardiotoxicity and Enhancing Anti‐Tumor Efficacy with a Metformin‐Integrated Self‐Assembled Nanomedicine
https://orcid.org/0000-0002-8399-6258
https://orcid.org/0000-0003-3794-661X
AbstractDoxorubicin (Dox) is a potent chemotherapeutic agent commonly used in cancer treatment. However, cardiotoxicity severely limited its clinical application. To address this challenge, a novel self‐assembled nanomedicine platform, PMDDH, is developed for the co‐delivery of Dox and metformin, an antidiabetic drug with cardioprotective and anti‐tumor properties. PMDDH integrates metformin into a polyethyleneimine‐based bioactive excipient (PMet), with Dox intercalated into double‐stranded DNA and a hyaluronic acid (HA) coating to enhance tumor targeting. The PMDDH significantly improves the pharmacokinetics and tumor‐targeting capabilities of Dox, while metformin enhances the drug's anti‐tumor activity by downregulating programmed cell death ligand 1 (PD‐L1) and activating the AMP‐activated protein kinase (AMPK) signaling pathway. Additionally, the DNA component stimulates the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway, which synergizes with Dox‐induced immunogenic cell death (ICD) to promote a robust anti‐tumor immune response. PMDDH markedly reduces Dox‐induced cardiotoxicity by preserving mitochondrial function, reducing reactive oxygen species (ROS) production, and inducing protective autophagy in cardiomyocytes. These findings position PMDDH as a promising dual‐function nanomedicine that enhances the anti‐tumor efficacy of Dox while minimizing its systemic toxicity, offering a safer and more effective alternative for cancer therapy.
Mitigating Doxorubicin‐Induced Cardiotoxicity and Enhancing Anti‐Tumor Efficacy with a Metformin‐Integrated Self‐Assembled Nanomedicine
https://orcid.org/0000-0002-8399-6258
https://orcid.org/0000-0003-3794-661X
AbstractDoxorubicin (Dox) is a potent chemotherapeutic agent commonly used in cancer treatment. However, cardiotoxicity severely limited its clinical application. To address this challenge, a novel self‐assembled nanomedicine platform, PMDDH, is developed for the co‐delivery of Dox and metformin, an antidiabetic drug with cardioprotective and anti‐tumor properties. PMDDH integrates metformin into a polyethyleneimine‐based bioactive excipient (PMet), with Dox intercalated into double‐stranded DNA and a hyaluronic acid (HA) coating to enhance tumor targeting. The PMDDH significantly improves the pharmacokinetics and tumor‐targeting capabilities of Dox, while metformin enhances the drug's anti‐tumor activity by downregulating programmed cell death ligand 1 (PD‐L1) and activating the AMP‐activated protein kinase (AMPK) signaling pathway. Additionally, the DNA component stimulates the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway, which synergizes with Dox‐induced immunogenic cell death (ICD) to promote a robust anti‐tumor immune response. PMDDH markedly reduces Dox‐induced cardiotoxicity by preserving mitochondrial function, reducing reactive oxygen species (ROS) production, and inducing protective autophagy in cardiomyocytes. These findings position PMDDH as a promising dual‐function nanomedicine that enhances the anti‐tumor efficacy of Dox while minimizing its systemic toxicity, offering a safer and more effective alternative for cancer therapy.
Mitigating Doxorubicin‐Induced Cardiotoxicity and Enhancing Anti‐Tumor Efficacy with a Metformin‐Integrated Self‐Assembled Nanomedicine
https://orcid.org/0000-0002-8399-6258
https://orcid.org/0000-0003-3794-661X
AbstractDoxorubicin (Dox) is a potent chemotherapeutic agent commonly used in cancer treatment. However, cardiotoxicity severely limited its clinical application. To address this challenge, a novel self‐assembled nanomedicine platform, PMDDH, is developed for the co‐delivery of Dox and metformin, an antidiabetic drug with cardioprotective and anti‐tumor properties. PMDDH integrates metformin into a polyethyleneimine‐based bioactive excipient (PMet), with Dox intercalated into double‐stranded DNA and a hyaluronic acid (HA) coating to enhance tumor targeting. The PMDDH significantly improves the pharmacokinetics and tumor‐targeting capabilities of Dox, while metformin enhances the drug's anti‐tumor activity by downregulating programmed cell death ligand 1 (PD‐L1) and activating the AMP‐activated protein kinase (AMPK) signaling pathway. Additionally, the DNA component stimulates the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway, which synergizes with Dox‐induced immunogenic cell death (ICD) to promote a robust anti‐tumor immune response. PMDDH markedly reduces Dox‐induced cardiotoxicity by preserving mitochondrial function, reducing reactive oxygen species (ROS) production, and inducing protective autophagy in cardiomyocytes. These findings position PMDDH as a promising dual‐function nanomedicine that enhances the anti‐tumor efficacy of Dox while minimizing its systemic toxicity, offering a safer and more effective alternative for cancer therapy.
Mitigating Doxorubicin‐Induced Cardiotoxicity and Enhancing Anti‐Tumor Efficacy with a Metformin‐Integrated Self‐Assembled Nanomedicine
Advanced Science
Huang, Jiaxin (Autor:in) / Yang, Jieru (Autor:in) / Yang, Yuanying (Autor:in) / Lu, Xiaofeng (Autor:in) / Xu, Juan (Autor:in) / Lu, Shan (Autor:in) / Pan, Hong (Autor:in) / Zhou, Wenhu (Autor:in) / Li, Wenqun (Autor:in) / Chen, Songwen (Autor:in)
07.03.2025
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
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