RESUMEN
Chemodynamic therapy (CDT) has emerged as a promising approach for treating infected diabetic wounds, while reliable imaging technology for simultaneous monitoring of ROS and therapeutic processes is still a formidable challenge. Herein, smart covalent organic framework (COF) nanoreactors (COF NRs) are constructed by hyaluronic acid (HA) packaged glucose oxidase (GOx) covalently linked Fe-COF for diabetic wound healing. Upon the breakdown of the HA protective layer, GOx consumes glucose to produce gluconic acid and hydrogen peroxide (H2O2), resulting in decreased local pH and H2O2 supplementation. Density functional theory (DFT) calculations show that Fe-COF has high catalytic activity towards H2O2, leading to in situ generation of hydroxyl radicals (·OH) for sterilization, and the localized downregulation of glucose effectively improved the microenvironment of diabetic wounds. Meanwhile, based on the near-infrared photothermal imaging of oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), the authors showed that TMB can be applied for the point-of-care testing of ·OH and glucose, and assessing the sterilization progress in vivo. More significantly, the facile photothermal signaling strategy can be extended to monitor various ROS-mediated therapeutic systems, enabling accurate prediction of treatment outcomes.
Asunto(s)
Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Peróxido de Hidrógeno/química , Esterilización/métodos , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Ratones , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , GlucosaRESUMEN
Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.
Asunto(s)
Ácido Hialurónico , Estructuras Metalorgánicas , Porfirinas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Porfirinas/química , Porfirinas/farmacología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Piel/efectos de los fármacos , Humanos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Hierro/química , Fotoquimioterapia/métodos , HialuronoglucosaminidasaRESUMEN
This study develops a systematic modeling framework, comprising a prediction model, a super-SBM model, and a spatial autocorrelation analysis model, to explore the spatial-temporal evolution tendencies of development efficiency within China's 30 regions in the low-carbon sports industry from 2006 to 2025. This framework aims to provide theoretical insights for the formulation of more targeted policies. Based on the empirical findings, the main conclusions of this study are as follows: (1) The optimal buffer operator grey prediction model demonstrates the highest accuracy among the prediction models examined. (2) The development efficiency curves of the 30 regions exhibit a significant increasing trend from 2006 to 2021, with values generally peaking between 0.4 and 0.6. (3) Notably, the disparity in development efficiency between developed and less developed regions is expected to progressively widen. (4) The development efficiency of the low-carbon sports industry across the 30 regions typically displays high-high clustering and low-low clustering during China's four five-year plan periods. This underscores the importance and urgency of promoting regional coordinated development within the low-carbon sports industry.
RESUMEN
Nano-induced endothelial leakiness (NanoEL) can improve the ability of nanoparticles (NPs) to enter the tumor environment, nevertheless, it can inadvertently trigger adverse effects such as tumor metastasis. To overcome these concerns, it becomes important to develop a NPs design strategy that capitalizes on the NanoEL effect while averting unwanted side effects during the drug delivery process. Herein, we introduce the PLGA-ICG-PEI-Ang1@M NP which has a core comprising poly (lactic-co-glycolic acid) (PLGA) and the inner shell with a highly positively charged polyethyleneimine (PEI) and the anti-permeability growth factor Angiopoietin 1 (Ang1), while the outer shell is camouflaged with a Jurkat cell membrane. During the drug delivery process, our NPs exhibit their capability to selectively target and penetrate endothelial cell layers. Once the NPs penetrate the endothelial layer, the proton sponge effect triggered by PEI in the acidic environment surrounding the tumor site can rupture the cell membrane on the NPs' surface. This rupture, in turn, enables the positively charged Ang1 to be released due to the electrostatic repulsion from PEI and the disrupted endothelial layer can be restored. Consequently, the designed NPs can penetrate endothelial layers, promote the cell layer recovery, restrict the tumor metastasis, and facilitate efficient cancer therapy. STATEMENT OF SIGNIFICANCE.