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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]

As one of the most significant imaging modalities currently available, magnetic resonance imaging (MRI) has been extensively utilized for clinically accurate cancer diagnosis. However, low signal-to-noise ratio (SNR) and low specificity for tumors continue to pose significant challenges. Inspired by the distance-dependent magnetic resonance tuning (MRET) phenomenon, the tumor microenvironment (TME)-activated off–on T1–T2 dual-mode MRI nanoswitch is presented in the current study to realize the sensitive early diagnosis of tumors. The tumor-specific nanoswitch is designed and manufactured on the basis of PDGFB-conjugating ferroferric oxide coated by Mn-doped silica (PDGFB-FMS), which can be degraded under the high-concentration GSH and low pH in TME to activate the T1–T2 dual-mode MRI signals. The tumor-specific off–on dual-mode MRI nanoswitch can significantly improve the SNR and is used successfully for the accurate diagnosis of early-stage tumors, particularly for orthotopic prostate cancer. In addition, the systemic delivery of the nanoswitch did not cause blood or tissue damage, and it can be excreted out of the body in a timely manner, demonstrating excellent biosafety. Overall, the strategy is a significant step in the direction of designing off–on dual-mode MRI nanoprobes to improve imaging accuracy, which opens up new avenues for the development of new MRI probes. [ABSTRACT FROM AUTHOR]

Researchers have identified a protein produced by mammalian cells that pumps drugs out of the cell. The protein, MRP4, could explain why some HIV patients become resistant to some AIDS drugs even though their viral isolate shows no sign of drug resistance.

Nicotinamide adenine dinucleotide (NADH) plays a pivotal role in metabolism. Convenient detection of NADH and its related metabolites has the pursuit of point-of-care and clinical analysis. Here, we propose a polymer dots (Pdots)-based NADH-sensitive electrochemiluminescence (ECL) biosensor for detection of NADH and three metabolites. Pdots acted as the efficient ECL emitters without additional modification to construct this biosensor. Specially, NADH both acted as the final detection target and at the same time as the bio-coreactants to sensitively influence the ECL intensities, in which NADH was generated or consumed in the presence of the target analyte and their specific enzyme. For glucose and lactic acid detection, NAD+ was reduced to NADH to generate an enhanced ECL signal. Conversely, for pyruvate detection, NADH was consumed to further decrease the ECL. The designed Pdots-based ECL biosensor showed wide detection ranges, high selectivity and low limits of detection of 4.6 μM, 0.7 μM and 0.5 μM for the analysis of three analytes, respectively. This strategy was successfully applied in quantifying the concentrations of glucose, lactic acid and pyruvate in human serum, which also has the potential to be implemented as a powerful and fast tool for ECL sensing of NADH and other related metabolites for point-of-care use and disease monitoring. [Display omitted] • A polymer dot-based NADH-sensitive electrochemiluminescent biosensor is developed. • The biosensor realized convenient and universal analysis of multiple metabolites. • The biosensor had high sensitivity and wide detection range for three metabolites. • The strategy is competent for target analysis in the serum samples. [ABSTRACT FROM AUTHOR]