Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks.

Normal life requires cell division to produce new cells, but cell death is necessary to maintain balance. Dysregulation of cell death can lead to the survival and proliferation of abnormal cells, promoting tumor development. Unlike apoptosis, necrosis, and autophagy, the newly recognized forms of regulated cell death (RCD) cuproptosis, ferroptosis, and PANoptosis provide novel therapeutic strategies for tumor treatment. Increasing research indicates that the death of tumor and immune cells mediated by these newly discovered forms of cell death can regulate the tumor microenvironment (TME) and influence the effectiveness of tumor immunotherapy. This review primarily elucidates the molecular mechanisms of cuproptosis, ferroptosis, and PANoptosis and their complex effects on tumor cells and the TME. This review also summarizes the exploration of nanoparticle applications in tumor therapy based on in vivo and in vitro evidence derived from the induction or inhibition of these new RCD pathways.

Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO₂ sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e⁻/h⁺) separation. More importantly, the presence of Mn⁴⁺ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H₂O₂ into O₂ for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.

Background: Radiofrequency ablation (RFA) is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality. Understanding the biological process related with RFA treatment is important for improving treatment strategy. This study aimed to identify the critical targets for regulating the efficacy of RFA. Methods: The RFA treatment in hepatocellular carcinoma (HCC) tumor models in vivo, was analyzed by RNA sequencing technology. The heat treatment in vitro for HCC tumor cells was also constructed to explore the mechanism after RFA treatment in tumor cells. Nanoparticles with high affinity to tumor cells were applied as a new therapy to interfere with the expression of maternal embryonic leucine zipper kinase (MELK). Results: It was found that RFA treatment upregulated MELK expression, and MELK inhibition promoted RFA efficacy by immunogenic cell death and the antitumor response, including anti-tumoral macrophage polarization and increased CD8 ⁺ T cell cytotoxicity in HCC. Mechanically, MELK binds to fatty acid-binding protein 5 (FABP5), and affects its ubiquitination through the K48R pathway to increase its stability, thereby activating protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling axis to weaken the RFA-mediated antitumor effect. In addition, the synthesis of arginylglycylaspartic acid (RGD)-lipid nanoparticles (LNPs) targeting tumor cell-intrinsic MELK enhanced RFA efficacy in HCC. Conclusion: MELK is a therapeutic target by regulating RFA efficacy in HCC, and targeting MELK via RGD-LNPs provides new insight into improving RFA efficacy in HCC clinical treatment and combating the malignant progression of liver cancer.

Radiofrequency ablation (RFA) has emerged as a critical therapeutic modality for hepatocellular carcinoma (HCC). Biomimetic magnetic nanoparticles further augment RFA efficacy by enhancing targeting precision and biocompatibility. This study introduces a novel nanocarrier co‐delivery system aimed at key molecular targets in HCC to amplify ferroptosis and reprogram intratumoral immunity, thereby improving the therapeutic outcomes of RFA. The proposed nanocarrier integrates cyclic arginine‐glycine‐aspartic acid (cRGD) and red blood cell membrane (RBCM), encapsulating superparamagnetic iron oxide (SPIO) to specifically target fatty acid‐binding protein 5 (FABP5) in tumor cells. Leveraging the superparamagnetic properties of SPIO, these nanoparticles enable real‐time monitoring and tracking through MRI. In vitro heat treatment of HCC cells simulates the RFA environment, while experiments employing the ferroptosis inhibitor Lipro1 conclusively demonstrate that the nanocarrier exerts anti‐tumor effects primarily through ferroptosis induction. Additionally, the impact on immunotherapy is underscored by combining the nanocarrier with anti‐PD‐L1 monoclonal antibodies. FABP5 overexpression in HCC tissues is strongly linked to RFA response. Targeting FABP5 using co‐delivery nanocarriers significantly enhances RFA efficacy. Furthermore, FABP5 deletion potentiates RFA‐induced ferroptosis and bolsters anti‐tumor immune responses, characterized by increased infiltration of CD8+ T cells and effector memory T cells, contributing to pronounced systemic anti‐tumor effects. Mechanistically, FABP5 inhibition activates the STING/TBK1 signaling pathway and modulates TBK1 protein stability. Notably, the nanocarrier system targeting FABP5 elevates PD‐L1 expression, and the combination of RFA with anti‐PD‐L1 therapy demonstrates synergistic efficacy against HCC. In conclusion, the FABP5‐targeting nanocarrier co‐delivery system offers a promising strategy to enhance RFA effectiveness in HCC, providing a novel framework for advancing clinical treatment approaches.

This study aimed to develop and validate a nomogram to predict both the tumor-stroma ratio (TSR) and the overall survival (OS) of patients with pancreatic ductal adenocarcinoma (PDAC) using preoperative dual-energy computed tomography (DECT) parameters. 153 patients with histopathologically confirmed PDAC who underwent preoperative DECT scans were retrospectively reviewed and divided into high- and low-TSR groups based on histological analyses of surgical specimens. Several DECT parameters of the primary tumor were measured, including the normalized iodine concentration (NIC), effective atomic number, slope of the energy spectrum attenuation curve (K), CT values (40–100 keV), and extracellular volume fraction (ECVf), and analyzed alongside clinical and radiological data. Univariate and multivariate logistic regression models were used to identify independent predictors, which were then incorporated into radiology, DECT, and nomogram models. The association of the nomograms with OS was assessed using Kaplan–Meier curves and Cox regression analysis. CT-reported lymph node status, NICvenous, Kvenous, and ECVf were identified as independent predictors of the TSR and included in the nomogram model. The nomogram demonstrated high predictive accuracy with an area under the receiver operating characteristic curve of 0.934 in the training set and 0.891 in the validation set, outperforming the radiology model (0.715 and 0.692, respectively). Patients with a high predicted TSR exhibited worse OS than those with a low predicted TSR. The DECT-based nomogram model provides a noninvasive and accurate preoperative prediction of the TSR and prognosis of patients with PDAC and may assist in individualized risk stratification and treatment planning.