Pegylated thrombopoietin mimetic peptide

Radiation-induced lung injury (RILI) initiates radiation pneumonitis and progresses to fibrosis as the main side effect experienced by patients with lung cancer treated with radiotherapy. There is no effective drug for RILI. Sustained vascular activation is a major contributor to the establishment of chronic disease. Here, using a whole thoracic irradiation (WTI) mouse model, we investigated the mechanisms and effectiveness of thrombopoietin mimetic (TPOm) for preventing RILI. We demonstrated that administering TPOm 24 hours before irradiation decreased histologic lung injury score, apoptosis, vascular permeability, expression of proinflammatory cytokines, and neutrophil infiltration in the lungs of mice 2 weeks after WTI. We described the expression of c-MPL, a TPO receptor, in mouse primary pulmonary microvascular endothelial cells, showing that TPOm reduced endothelial cell-neutrophil adhesion by inhibiting ICAM-1 expression. Seven months after WTI, TPOm-treated lung exhibited less collagen deposition and expression of MMP-9, TIMP-1, IL-6, TGF-β, and p21. Moreover, TPOm improved lung vascular structure, lung density, and respiration rate, leading to a prolonged survival time after WTI. Single-cell RNA sequencing analysis of lungs 2 weeks after WTI revealed that TPOm shifted populations of capillary endothelial cells toward a less activated and more homeostatic phenotype. Taken together, TPOm is protective for RILI by inhibiting endothelial cell activation.

Despite the advantages of high tissue penetration depth, selectivity, and non‐invasiveness of photothermal therapy for cancer treatment, developing NIR‐II photothermal agents with desirable photothermal performance and advanced theranostics ability remains a key challenge. Herein, a universal surface modification strategy is proposed to effectively improve the photothermal performance of vanadium carbide MXene nanosheets (L‐V2C) with the removal of surface impurity ions and generation of mesopores. Subsequently, MnOx coating capable of T1‐weighted magnetic resonance imaging can be in situ formed through surface redox reaction on L‐V2C, and then, stable nanoplatforms (LVM‐PEG) under physiological conditions can be obtained after further PEGylation. In the tumor microenvironment irradiated by NIR‐II laser, multivalent Mn ions released from LVM‐PEG, as a reversible electronic station, can consume the overexpression of glutathione and catalyze a Fenton‐like reaction to produce ·OH, resulting in synchronous cellular oxidative damage. Efficient synergistic therapy promotes immunogenic cell death, improving tumor‐related immune microenvironment and immunomodulation, and thus, LVM‐PEG can demonstrate high accuracy and excellent anticancer efficiency guided by multimodal imaging. As a result, this study provides a new approach for the customization of 2D surface strategies and the study of synergistic therapy mechanisms, highlighting the application of MXene‐based materials in the biomedical field.