Search

Currently, there is no effective treatment for chronic skin radiation injury, which burdens patients significantly. Previous studies have shown that cold atmospheric plasma has an apparent therapeutic effect on acute and chronic skin injuries in clinical. However, whether CAP is effective for radiation-induced skin injury has not been reported. We created 35Gy X-ray radiation exposure within 3 * 3 cm 2 region of the left leg of rats and applied CAP to the wound bed. Wound healing, cell proliferation and apoptosis were examined in vivo or vitro. CAP alleviated radiation-induced skin injury by enhancing proliferation and migration and cellular antioxidant stress and promoting DNA damage repair through regulated nuclear translocation of NRF2. In addition, CAP inhibited the proinflammatory factors' expression of IL-1β, TNF-α and temporarily increased the pro repair factor's expression of IL-6 in irradiated tissues. At the same time, CAP also changed the polarity of macrophages to a repair-promoting phenotype. Our finding suggested that CAP ameliorated radiation-induced skin injury by activating NRF2 and ameliorating the inflammatory response. Our work provided a preliminary theoretical foundation for the clinical administration of CAP in high-dose irradiated skin injury., Competing Interests: Declaration of competing interest The authors declare no conflict of interest and any commercial affiliations., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Radiation-induced pulmonary fibrosis (RIPF) is a common complication during thoracic radiotherapy, but there are few effective treatments. Here, we identify IR-780, a mitochondria-targeted near-infrared (NIR) dye, can selectively accumulate in the irradiated lung tissues. Besides, IR-780 significantly alleviates radiation-induced acute lung injury and fibrosis. Furthermore, our results show that IR-780 prevents the differentiation of fibroblasts and the release of pro-fibrotic factors from alveolar macrophages induced by radiation. Besides, IR-780 downregulates the expression of glycolysis-associated genes, and 2-Deoxy-d-glucose (2-DG) also prevents the development of fibrosis in vitro, suggesting radioprotective effects of IR-780 on RIPF might be related to glycolysis regulation. Finally, IR-780 induces tumour cell apoptosis and enhances radiosensitivity in representative H460 and A549 cell lines. These findings indicate that IR-780 is a potential therapeutic small-molecule dye during thoracic radiotherapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Mesenchymal stromal cells (MSCs) have been developed for the prevention and treatment of graft-versus-host disease (GVHD). Non-cultured natural MSCs are considered ideal, as they better maintain their biological and therapeutic properties. The skin is the largest organ in the body and constitutes an interesting alternative to bone marrow for the generation of MSCs. Large numbers of dermal-derived-MSCs (DMSCs) can be easily generated without culturing in vitro, but their therapeutic effects still remain unclear. In this study, we described for the first time the use of non-cultured DMSCs for controlling GVHD in an MHC-mismatched mouse model and investigated their immunomodulatory effects. Our results showed that non-cultured mouse DMSCs decreased the incidence and severity of acute GVHD during MHC-mismatched stem cell transplantation in mice. This effect was mediated by the inhibition of splenic cell (SPC) proliferation and the enhancement of Treg cells. Consistent with the results in vivo, the results in vitro showed that human DMSCs inhibited the proliferation of peripheral blood mononuclear cells (PBMCs) by inhibiting the proliferation of CD3(+) T cells. hDMSCs prevented PBMCs from entering S phase, suppressed the activation of CD3(+) T cells and increased Treg proportions. In conclusion, DMSCs should be considered as a novel MSC source for the control of refractory GVHD., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Personalized oncology significantly relies on the development of theranostic agents to integrate cancer therapeutics and diagnostics. Current strategy for development of such multifunctional agents requires multistep chemical conjugation with cancer specific ligands, contrast agents and therapeutic drugs. In this study, we reported a near infrared (NIR) heptamethine indocyanine dye, IR-780, which selectively accumulated in the mitochondria of drug-resistant human lung cancer cells (A549/DR) and significantly inhibited cell growth, self-renewal and migration without the need of any chemical conjugation. IR-780 was also able to induce A549/DR cell apoptosis by disrupting the mitochondrial function. Furthermore, IR-780 dye exhibited remarkable tumoricidal activity and inhibited tumor recurrence in mouse syngeneic Lewis lung carcinoma xenograft model. With the unique properties of targeting, near infrared imaging and inhibitive effect to the drug-resistant cancer cells both in vitro and in vivo, IR-780 may represent a potential theranostic agent for tumor recurrence., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

IR-780 iodide, a near-infrared fluorescent heptamethine dye, has been recently characterized to exhibit preferential accumulation property in the mitochondria of tumor cells. In this study, we investigated the possible mechanisms for its tumor selective activity and its potential as a drug delivery carrier. Results showed that the energy-dependent uptake of IR-780 iodide into the mitochondria of tumor cells was affected by glycolysis and plasma membrane potential. Moreover, OATP1B3 subtype of organic anion transporter peptides (OATPs) may play a dominant role in the transportation of IR-780 iodide into tumor cells, while cellular endocytosis, mitochondrial membrane potential and the ATP-binding cassette transporters did not show significant influence to its accumulation. We further evaluated the potential of IR-780 iodide as a drug delivery carrier by covalent conjugation of IR-780 with nitrogen mustard (IR-780NM). In vivo imaging showed that IR-780NM remained the tumor targeting property, indicating that IR-780 iodide could be potentially applied as a drug delivery agent for cancer targeted imaging and therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Personalized oncology significantly relies on the development of cancer theranostic agents to integrate cancer therapeutics and diagnostics. Current most common strategy for development of such multifunctional agents requires multistep chemical conjugation with cancer targeted ligands, contrast agents and therapeutic agents. Here we report the chemical synthesis and biological characterization of a new heptamethine dye, termed as IR-808DB, natively with multifunctional characteristics of cancer targeting, near-infrared fluorescence imaging, and efficient anticancer activity. The tumor inhibition effect of IR-808DB is higher than that of cyclophosphamide (CTX) toward a broad spectrum of tumor xenograft models. These findings provide IR-808DB a promising prospect as a new cancer theranostic agent that would enable integration of cancer targeted therapeutics and diagnostics without requirement of multi-component chemical conjugation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The future personalized oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging, and cytotoxic activities. In our recent study, we have recently identified a near infrared fluorescent heptamethine dye, IR-780, with unexpected preferential accumulation in a broad spectra of tumor cells for in vivo tumor targeting and imaging. On the basis of this foregoing work, in this study, we describe here the chemical synthesis and biological characterization of an analog of IR-780, termed as IR-808, which not only possesses similar tumor targeting and imaging properties of IR-780, but also has unique photodependent cytotoxic activity. In addition, IR-808 also exhibits favorable optical and pharmacokinetic properties, as well as good biocompatibility. This dye may hold promise as a candidate multifunctional theranostic agent for future tumor targeted imaging and photodynamic therapy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The development of multifunctional agents for simultaneous tumor targeting and near infrared (NIR) fluorescence imaging is expected to have significant impact on future personalized oncology owing to the very low tissue autofluorescence and high tissue penetration depth in the NIR spectrum window. Cancer NIR molecular imaging relies greatly on the development of stable, highly specific and sensitive molecular probes. Organic dyes have shown promising clinical implications as non-targeting agents for optical imaging in which indocyanine green has long been implemented in clinical use. Recently, significant progress has been made on the development of unique NIR dyes with tumor targeting properties. Current ongoing design strategies have overcome some of the limitations of conventional NIR organic dyes, such as poor hydrophilicity and photostability, low quantum yield, insufficient stability in biological system, low detection sensitivity, etc. This potential is further realized with the use of these NIR dyes or NIR dye-encapsulated nanoparticles by conjugation with tumor specific ligands (such as small molecules, peptides, proteins and antibodies) for tumor targeted imaging. Very recently, natively multifunctional NIR dyes that can preferentially accumulate in tumor cells without the need of chemical conjugation to tumor targeting ligands have been developed and these dyes have shown unique optical and pharmaceutical properties for biomedical imaging with superior signal-to-background contrast index. The main focus of this article is to provide a concise overview of newly developed NIR dyes and their potential applications in cancer targeting and imaging. The development of future multifunctional agents by combining targeting, imaging and even therapeutic routes will also be discussed. We believe these newly developed multifunctional NIR dyes will broaden current concept of tumor targeted imaging and hold promise to make an important contribution to the diagnosis and therapeutics for the treatment of cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Failure to cure many cancers once they are disseminated has been attributed to the presence of resistant cancer stem cells. Cantharidin, a natural compound isolated from the beetles and other insects has been traditionally used as anticancer agent, but limited by its significant toxicity. It has shown that cantharidin can force cancer cells prematurely into cell cycle and subsequently induce apoptotic cell death through the inhibition of protein phosphatase 2A (PP2A). In this study, we showed that a synthesized analog of cantharidin, LB1, with significant PP2A inhibition activity but without apparent toxicity, greatly enhanced the effectiveness of the standard anti-sarcoma chemotherapeutic agent, doxorubicin (DOX), in the xenograft growth inhibition and lung metastases prevention of an aggressive sarcoma derived from transformed mesenchymal stem cells in syngeneic rats. We report here on the possibility of, pharmacologic inhibition of PP2A with low toxicity cantharidin derivatives may be a useful strategy to enhance the effectiveness of DNA-damaged chemotherapeutic drugs against stem cell-derived cancer., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Near-infrared (NIR) fluorescence imaging holds great promise for tumor imaging due to low tissue autofluorescence and deep tissue penetration. However, most tumor-targeting fluorescent probes require combination of targeting agents and fluorescent reporters. In this study, we described a NIR heptamethine cyanine dye, IR-780 iodide, with preferential accumulation in multiple tumor cells without the necessity of chemical conjugation. The IR-780 iodide was found to retain in tumors but not normal cells in multiple tumor xenografts in nude mice and chemically-induced lung tumors in C57BL/6 mice. The fluorescent signal of tumors could persist at least 20 days with a significant signal-to-background ratio. As a lipophilic cation, a predominant accumulation of IR-780 iodide was shown in the mitochondria of tumor cells owing to the high magnitude of mitochondrial membrane potential in tumor cells than normal cells. We further showed that the transportation of IR-780 iodide into tumor cells was mediated by the organic anion transporter peptides (OATPs) because the dye accumulation was significantly inhibited by sulfobromophthalein (BSP), a competitive inhibitor of OATPs. Our study shows that IR-780 iodide that preferentially accumulates in tumor cells and is natively NIR fluorescent would be useful in tumor detection., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

We describe a near-infrared fluorescent heptamethine dye (IR-780 iodide) with unique properties for sentinel lymph node (SLN) mapping in both small and large animals. This dye has a significant photobrightening effect in serum and a long retention time in the lymphatic system which allows to acquire much higher signal-to-noise ratios. Injection of only 10 nmol of this dye permits SLNs to be imaged easily in pigs using excitation fluence rates of only 2 microW/cm(2). In addition, this dye has a unique stability property after formalin fixation in tissues which raises the possibility of developing new and sensitive means of detecting lymph nodes in harvested surgical specimens. This dye can be completely cleared from the circulation in a couple of days and does not cause acute systemic toxicity., ((c) 2009 Elsevier Ltd. All rights reserved.)

Objectives: To visualize human prostate cancer cells in mouse bone with bioconjugated near-infrared quantum dot (QD) probes. Near-infrared fluorescent probes using QDs can visualize tumors in deep tissues in vivo., Methods: Human prostate cancer C4-2B xenografts grown in mouse tibia were detected by prostate-specific membrane antigen antibody conjugated with QDs emitting light at the near-infrared range of 800 nm (QD800). Images in culture and in vivo were acquired using the IVIS Imaging System., Results: As few as 5000 cells can be detected subcutaneously when tagged with QD800 conjugate and injected directly into mice. QD800 conjugate injected intravenously in mice harboring C4-2B tumors in tibia detected signals from a minimum of 500 000 cells. The maximal light emission was detected 30 minutes after intravenous injection of QD800 conjugate in mice with established C4-2B tumors., Conclusions: Bioconjugated near-infrared QD probes are highly sensitive molecular imaging tools for human prostate cancer micrometastases in mice.