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      Efficient Therapy of Inflammatory Bowel Disease (IBD) with Highly Specific and Durable Targeted Ta 2C Modified with Chondroitin Sulfate (TACS)

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          Abstract

          Non‐invasive localization of lesions and specific targeted therapy are still the main challenges for inflammatory bowel disease (IBD). Ta, as a medical metal element, has been widely used in the treatment of different diseases because of its excellent physicochemical properties but is still far from being explored in IBD. Here, Ta 2C modified with chondroitin sulfate (CS) (TACS) is evaluated as a highly targeted therapy nanomedicine for IBD. Specifically, TACS is modified with dual targeting CS functions due to IBD lesion‐specific positive charges and high expression of CD44 receptors. Thanks to the acid stability, sensitive CT imaging function, and strong reactive oxygen species (ROS) elimination ability, oral TACS can accurately locate and delineate IBD lesions through non‐invasive CT imaging, and specifically targeted treat IBD effectively because high levels of ROS are a central factor in the progression of IBD. As expected, TACS has much better imaging and therapeutic effects than clinical CT contrast agent and first‐line drug 5‐aminosalicylic acid, respectively. The mechanism of TACS treatment mainly involves protection of mitochondria, elimination of oxidative stress, inhibiting macrophage M1 polarization, protection of intestinal barrier, and restoration of intestinal flora balance. Collectively, this work provides unprecedented opportunities for oral nanomedicines to targeted therapy of IBD.

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          Most cited references73

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          Mitochondria as multifaceted regulators of cell death

          Through their many and varied metabolic functions, mitochondria power life. Paradoxically, mitochondria also have a central role in apoptotic cell death. Upon induction of mitochondrial apoptosis, mitochondrial outer membrane permeabilization (MOMP) usually commits a cell to die. Apoptotic signalling downstream of MOMP involves cytochrome c release from mitochondria and subsequent caspase activation. As such, targeting MOMP in order to manipulate cell death holds tremendous therapeutic potential across different diseases, including neurodegenerative diseases, autoimmune disorders and cancer. In this Review, we discuss new insights into how mitochondria regulate apoptotic cell death. Surprisingly, recent data demonstrate that besides eliciting caspase activation, MOMP engages various pro-inflammatory signalling functions. As we highlight, together with new findings demonstrating cell survival following MOMP, this pro-inflammatory role suggests that mitochondria-derived signalling downstream of pro-apoptotic cues may also have non-lethal functions. Finally, we discuss the importance and roles of mitochondria in other forms of regulated cell death, including necroptosis, ferroptosis and pyroptosis. Collectively, these new findings offer exciting, unexplored opportunities to target mitochondrial regulation of cell death for clinical benefit.
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            Ulcerative colitis

            Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. UC has evolved into a global burden given its high incidence in developed countries and the substantial increase in incidence in developing countries. An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. Since the early 2000s, anti-tumour necrosis factor (TNF) treatment has significantly improved treatment outcomes. Advances in medical treatments have enabled a paradigm shift in treatment goals from symptomatic relief to endoscopic and histological healing to achieve better long-term outcomes and, consequently, diagnostic modalities have also been improved to monitor disease activity more tightly. Despite these improvements in patient care, a substantial proportion of patients, for example, those who are refractory to medical treatment or those who develop colitis-associated colorectal dysplasia or cancer, still require restorative proctocolectomy. The development of novel drugs and improvement of the treatment strategy by implementing personalized medicine are warranted to achieve optimal disease control. However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.
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              A Two-Dimensional Biodegradable Niobium Carbide (MXene) for Photothermal Tumor Eradication in NIR-I and NIR-II Biowindows.

              Conventionally, ceramics-based materials, fabricated by high-temperature solid-phase reaction and sintering, are preferred as bone scaffolds in hard-tissue engineering because of their tunable biocompatibility and mechanical properties. However, their possible biomedical applications have rarely been considered, especially the cancer phototherapeutic applications in both the first and second near-infrared light (NIR-I and NIR-II) biowindows. In this work, we explore, for the first time as far as we know, a novel kind of 2D niobium carbide (Nb2C), MXene, with highly efficient in vivo photothermal ablation of mouse tumor xenografts in both NIR-I and NIR-II windows. The 2D Nb2C nanosheets (NSs) were fabricated by a facile and scalable two-step liquid exfoliation method combining stepwise delamination and intercalation procedures. The ultrathin, lateral-nanosized Nb2C NSs exhibited extraordinarily high photothermal conversion efficiency (36.4% at NIR-I and 45.65% at NIR-II), as well as high photothermal stability. The Nb2C NSs intrinsically feature unique enzyme-responsive biodegradability to human myeloperoxidase, low phototoxicity, and high biocompatibility. Especially, these surface-engineered Nb2C NSs present highly efficient in vivo photothermal ablation and eradication of tumor in both NIR-I and NIR-II biowindows. This work significantly broadens the application prospects of 2D MXenes by rationally designing their compositions and exploring related physiochemical properties, especially on phototherapy of cancer.
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                Author and article information

                Contributors
                Journal
                Advanced Materials
                Advanced Materials
                Wiley
                0935-9648
                1521-4095
                September 2023
                July 23 2023
                September 2023
                : 35
                : 36
                Affiliations
                [1 ] Department of Geriatric Surgery Xiangya Hospital Central South University Changsha 410008 China
                [2 ] Xiangya School of Pharmaceutical Sciences Central South University Changsha 410008 China
                [3 ] National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha 410008 China
                [4 ] Department of General Surgery Xiangya Hospital Central South University Changsha 410008 China
                [5 ] Department of Pharmacy, Xiangya Hospital Central South University Changsha 410008 P. R. China
                [6 ] Hubei Key Laboratory of Optical Information and Pattern Recognition Wuhan Institute of Technology Wuhan 430205 China
                [7 ] Department of Radiology Xiangya Hospital Central South University Changsha 410008 China
                [8 ] Department of Pathology Xiangya Hospital, Central South University Changsha 410008 China
                [9 ] Hunan Provincial Key Laboratory of Cardiovascular Research Xiangya School of Pharmaceutical Sciences Central South University Changsha 410008 China
                [10 ] Geriatric Medical Center People's Hospital of Ningxia Hui Autonomous Region Yinchuan 750002 China
                [11 ] Key Laboratory of Aging‐related Bone and Joint Diseases Prevention and Treatment. Ministry of Education Xiangya Hospital Central South University Changsha 410008 China
                Article
                10.1002/adma.202301585
                37224059
                8e1b8314-36cb-47b6-9c2f-42fbd1c77e61
                © 2023

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