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Chemotherapy is widely used to treat colorectal cancer (CRC). Despite its substantial benefits, the development of drug resistance and adverse effects remain challenging. This study aimed to elucidate a novel role of glucagon in anti‐cancer therapy. In a series of in vitro experiments, glucagon inhibited cell migration and tube formation in both endothelial and tumor cells. In vivo studies demonstrated decreased tumor blood vessels and fewer pseudo‐vessels in mice treated with glucagon. The combination of glucagon and chemotherapy exhibited enhanced tumor inhibition. Mechanistic studies demonstrated that glucagon increased the permeability of blood vessels, leading to a pronounced disruption of vessel morphology. Signaling pathway analysis identified a VEGF/VEGFR‐dependent mechanism whereby glucagon attenuated angiogenesis through its receptor. Clinical data analysis revealed a positive correlation between elevated glucagon expression and chemotherapy response. This is the first study to reveal a role for glucagon in inhibiting angiogenesis and vascular mimicry. Additionally, the delivery of glucagon‐encapsulated PEGylated liposomes to tumor‐bearing mice amplified the inhibition of angiogenesis and vascular mimicry, consequently reinforcing chemotherapy efficacy. Collectively, the findings demonstrate the role of glucagon in inhibiting tumor vessel network and suggest the potential utility of glucagon as a promising predictive marker for patients with CRC receiving chemotherapy. [ABSTRACT FROM AUTHOR]

The application of chemodynamic therapy (CDT) for cancer is a serious challenge owing to the low efficiency of the Fenton catalyst and insufficient H2O2 expression in cells. Herein, we fabricated a PDGFB targeting, biodegradable FePt alloy assembly for magnetic resonance imaging (MRI)-guided chemotherapy and starving-enhanced chemodynamic therapy for cancer using PDGFB targeting, pH-sensitive liposome-coated FePt alloys, and GOx (pLFePt-GOx). We found that the Fenton-catalytic activity of FePt alloys was far stronger than that of traditional ultrasmall iron oxide nanoparticle (UION). Upon entry into cancer cells, pLFePt-GOx nanoliposomes degraded into many tiny FePt alloys and released GOx owing to the weakly acidic nature of the tumor microenvironment (TME). The released GOx-mediated glucose consumption not only caused a starvation status but also increased the level of cellular H2O2 and acidity, promoting Fenton reaction by FePt alloys and resulting in an increase in reactive oxygen species (ROS) accumulation in cells, which ultimately realized starving-enhanced chemodynamic process for killing tumor cells. The anticancer mechanism of pLFePt-GOx involved ROS-mediated apoptosis and ferroptosis, and glucose depletion-mediated starvation death. In the in vivo assay, the systemic delivery of pLFePt-GOx showed excellent antitumor activity with low biological toxicity and significantly enhanced T2-weighted magnetic resonance imaging (MRI) signal of the tumor, indicating that pLFePt-GOx can serve as a highly efficient theranostic tool for cancer. This work thus describes an effective, novel multi-modal cancer theranostic system. [ABSTRACT FROM AUTHOR]

The application of chemodynamic therapy (CDT) for cancer is a serious challenge owing to the low efficiency of the Fenton catalyst and insufficient H2O2 expression in cells. Herein, we fabricated a PDGFB targeting, biodegradable FePt alloy assembly for magnetic resonance imaging (MRI)-guided chemotherapy and starving-enhanced chemodynamic therapy for cancer using PDGFB targeting, pH-sensitive liposome-coated FePt alloys, and GOx (pLFePt-GOx). We found that the Fenton-catalytic activity of FePt alloys was far stronger than that of traditional ultrasmall iron oxide nanoparticle (UION). Upon entry into cancer cells, pLFePt-GOx nanoliposomes degraded into many tiny FePt alloys and released GOx owing to the weakly acidic nature of the tumor microenvironment (TME). The released GOx-mediated glucose consumption not only caused a starvation status but also increased the level of cellular H2O2 and acidity, promoting Fenton reaction by FePt alloys and resulting in an increase in reactive oxygen species (ROS) accumulation in cells, which ultimately realized starving-enhanced chemodynamic process for killing tumor cells. The anticancer mechanism of pLFePt-GOx involved ROS-mediated apoptosis and ferroptosis, and glucose depletion-mediated starvation death. In the in vivo assay, the systemic delivery of pLFePt-GOx showed excellent antitumor activity with low biological toxicity and significantly enhanced T2-weighted magnetic resonance imaging (MRI) signal of the tumor, indicating that pLFePt-GOx can serve as a highly efficient theranostic tool for cancer. This work thus describes an effective, novel multi-modal cancer theranostic system. [ABSTRACT FROM AUTHOR]