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Spinal cord injury (SCI) is a devastating condition with limited efficacious treatment options. Recent research has revealed the potential of functional nanomedicines to inhibit ferroptosis and reduce inflammatory response, offering a promising therapeutic approach for SCI. Urolithin A (UA) exhibits outstanding antioxidant and anti-inflammatory properties in different neurodegenerative disorders. Intriguingly, whether UA can antagonize ferroptosis remains unknown, and its specific impact on SCI and underlying mechanisms have not been extensively explored. Given the pathological response of esterase overexpression in the SCI microenvironment, taken advantages of nanotechnology in precise targeted delivery, flexible structure design and effective enhancement of drug metabolism pathways, in this study, a novel silica-based integrated nanocarrier is constructed by incorporating carbamate-bridged UA into silica nanoparticles. The resulting PEGylated UA silicon hybrid NPs (PUASi NPs) are sensitive and could be specifically recognized and cleaved by esterase. The findings from both in vitro and in vivo experiments demonstrate that the continuous release of UA from PUASi NPs exhibits notable anti-ferroptotic and anti-inflammatory effects, thus contributing to the improvement of functional recovery in mice suffering from SCI. Collectively, this esterase-activatable nanoprodrug strategy offers an alternative therapeutic regimen for clinical intervention in SCI, with promising prospects for translation into clinical practice. [Display omitted] • PUASi NPs are sensitive and could be specifically recognized and cleaved by esterase. • The sustained release of UA not only inhibit ferroptosis but also protect neuronal cells from neuroinflammatory damage. • PUASi NPs promote nerve regeneration after SCI via reducing ferroptosis and reprogramming inflammatory microenvironment. [ABSTRACT FROM AUTHOR]

Multidrug resistance is one of the greatest challenges in cancer therapy. Herein we described the synthesis of folate (FA)-conjugated selenium nanoparticles (SeNPs) as cancer-targeted nano-drug delivery system for ruthenium polypyridyl (RuPOP) exhibits strong fluorescence, which allows the direct imaging of the cellular trafficking of the nanosystem. This nanosystem could effectively antagonize against multidrug resistance in liver cancer. FA surface conjugation significantly enhanced the cellular uptake of SeNPs by FA receptor-mediated endocytosis through nystain-dependent lipid raft-mediated and clathrin-mediated pathways. The nanomaterials overcame the multidrug resistance in R-HepG2 cells through inhibition of ABC family proteins expression. Internalized nanoparticles triggered ROS overproduction and induced apoptosis by activating p53 and MAPKs pathways. Moreover, FA-SeNPs exhibited low in vivo acute toxicity, which verified the safety and application potential of FA-SeNPs as nanodrugs. This study provides an effective strategy for the design of cancer-targeted nanodrugs against multidrug resistant cancers. From the Clinical Editor In the combat against hepatocellular carcinoma, multidrug resistance remains one of the obstacles to be overcome. The authors designed and synthesized folate (FA)-conjugated selenium nanoparticles (SeNPs) with enhanced cancer-targeting capability. This system carried ruthenium polypyridyl (RuPOP), an efficient metal-based anti-cancer drug with strong fluorescence. It was shown that this combination was effective in antagonizing against multidrug resistance in vitro. [ABSTRACT FROM AUTHOR]

Abstract: A simple method for preparation of adenosine triphosphate (ATP) surface-functionalized selenium nanoparticles (SeNPs@ATP) with enhanced cell permeabilization and anticancer activity has been demonstrated in the study reported in this article. Spherical SeNPs were decorated with ATP by strong adsorption through an Se-N bond, leading to the highly stable structure of the conjugates. ATP surface decoration significantly enhanced the cellular uptake and anticancer activity of SeNPs. Induction of apoptosis in HepG2 human hepatocellular carcinoma cells by SeNPs@ATP was evidenced by accumulation of the sub-G1 cell population, phosphatidylserine exposure, DNA fragmentation, PARP cleavage and caspase activation. Further studies found that SeNPs@ATP treatment triggered the depletion of mitochondrial membrane potential and reactive oxygen species (ROS) overproduction. Our results demonstrate that the use of ATP as a surface decorator of SeNPs is a novel strategy to achieve anticancer synergy. SeNPs@ATP may be a candidate for further evaluation as a chemotherapeutic agent for human cancers. From the Clinical Editor: In this paper, adenosine triphosphate (ATP) surface-functionalized selenium nanoparticles are discussed as cell-penetrating anticancer agents. Conjugates are stable and ATP functionalization greatly enhances the apoptosis induction properties of the selenium nanoparticles in HepG2 human hepatocellular carcinoma cells. [Copyright &y& Elsevier]

The use of metal complexes in cancer treatment is hampered by the insufficient accumulation in tumor regions and observable systemic toxicity due to their nonspecificity in vivo . Herein we present a cancer-targeted DNA origami as biocompatible nanocarrier of metal complexes to achieve advanced antitumor effect. The formation of unique tetrahedral nanostructure of DNA cages effectively enhances the interaction between ruthenium polypyridyl complexes (RuPOP) and the cages, thus increasing the drug loading efficacy. Conjugation of biotin to the DNA-based nanosystem (Bio-cage@Ru) enhances its specific cellular uptake, drug retention and cytotoxicity against HepG2 cells. Different from free RuPOP and the cage itself, Bio-cage@Ru translocates to cell nucleus after internalization, where it undergoes self-immolative cleavage in response to DNases, leading to triggered drug release and induction of ROS-mediated cell apoptosis. Moreover, in the nude mice model, the nanosystem specifically accumulates in tumor sites, thus exhibits satisfactory in vivo antitumor efficacy, and alleviates the damage of liver, kidney, lung and heart function of nude mice induced by RuPOP and tumor xenografts. Collectively, this study demonstrates a strategy for construction of biocompatible and cancer-targeted DNA origami with enhanced anticancer efficacy and reduced toxicity for next-generation cancer therapy. [ABSTRACT FROM AUTHOR]

Resistance of cancer to radiotherapy and/or chemotherapy is one of the important reasons of clinical treatment failure and recurrence. Chemoradiation is an optional method to over-coming of radioresistance and chemoresistance. Selenium nanoparticles (SeNPs) with special chemical and physical properties, has been identified as a novel nanocarrier and therapy agent with broad-spectrum anticancer activities due to generate ROS in cells. Herein, X-ray responsive selenium nanoparticles were facilely fabricated by using PEG as surface decorator and template. This nanosystem (PEG-SeNPs) demonstrated X-ray responsive property that was attributed to its amorphous characteristic. Interestingly, the nanosystem demonstrated significant radiosensitization effects with X-ray. Specifically, co-treatment of cancer cells with PEG-SeNPs and X-ray significantly and synergistically enhanced the cells growth inhibition through induction of cell apoptosis, as evidenced by DNA fragmentation and activation of caspase-3. In the cell model, we found that internalized nanoparticles could degrade upon X-ray exposure, which further confirm the X-ray responsive property of the nanoparticles. Moreover, the nanosystem could significantly induced intracellular ROS generation in a time-dependent manner, which peaked at about 40 min and gradually decreased thereafter. As a results, ROS overproduction led to mitochondria fragmentation and the cell apoptosis. Taken together, this study provides a novel strategy for rational design and facile synthesis of chemo-radio therapeutic radiosensitization nanomaterials. [ABSTRACT FROM AUTHOR]

This study not only provides a simple method for synthesis of a specific DNA-SeNPs, which is a simple and cost-saving nanosystem, for recognition and removal of anti-dsDNA autoantibodies both in serum from 128 clinically identified systemic lupus erythematosus (SLE) patients and kidney from 36 clinically identified lupus nephritis (LN) patients, but also sheds light on the possible action mechanisms of anti-dsDNA antibodies in the pathogenesis and progression of SLE. [Display omitted] • SLE-specific targeting DNA-SeNPs with perfect biocompatibility. • DNA-SeNPs highly efficient remove anti-dsDNA autoantibodies in serum of SLE patients. • DNA-SeNPs could visualize the distribution of anti-dsDNA antibodies in the LN. Systemic lupus erythematosus (SLE) with increasing morbidity and mortality rate is characterized by multisystem damage and diverse autoantibodies production, such as anti-double stranded (ds) DNA antibodies. It is noted that anti-dsDNA antibodies are essential in the pathogenesis and progression of SLE and lupus nephritis (LN), however; anti-dsDNA antibodies could not be specifically recognized and quickly removed in clinic. Therefore, it is urgently needed to develop SLE-specific targeting agents to improve the diagnose and treatment of SLE. Herein, a selenium nanosystem (DNA-SeNPs) with surface decoration of calf thymus DNA (ctDNA) was constructed to specifically recognize and remove anti-dsDNA autoantibodies in the serums of 128 SLE patients and in the kidneys of 36 LN patients. The nanotherapeutics exhibited perfect biocompatibility and safety in patients to directly eliminate anti-dsDNA antibodies. In addition, the clearance ratio of anti-dsDNA antibodies by DNA-SeNPs was notably higher than other products widely used in clinical practice, implying that the excellent removal efficiency of this nanotherapeutics. Importantly, DNA-SeNPs not only help to visualize the distribution of anti-dsDNA antibodies in the lesions of kidney, but also semi-quantify the deposition of these antibodies, which are the key cause of the local damage. To sum up, this study provides a simple approach for rational design of nanoscale SLE-targeting nanomedicine to improve the diagnose and treatment of SLE, also sheds light on the possible mechanisms of anti-dsDNA antibodies in the pathogenesis and progression of SLE. [ABSTRACT FROM AUTHOR]

Herein a bioactive component of mannose-rich oligosaccharides with potent anti-inflammatory capacity was employed to functionalize SeNPs to achieve high stability, biocompatibility and therapeutic potential by promoting macrophages reprogramming leading to inflammation resolution. This study not only provides strategy for functionalization of nanomedicines using structure-optimized MRO, but also reveals the action mechanism on successful treatment of IBD and other intestinal diseases. [Display omitted] • Bioactive mannose-rich oligosaccharides were produced by enzymatic hydrolysis. • Functionalized MRO-SeNPs reprograms macrophage towards M2 polarization. • MRO-SeNPs effectively alleviates DSS-induced colitis in mice. Inflammatory bowel disease (IBD) is a global disease and usually classified into Crohn's disease (CD) and ulcerative colitis (UC), in which the inflammatory response is known to play a pivotal role. Herein, a bioactive component of mannose-rich oligosaccharides (MRO) was produced by enzymatic hydrolysis with most potent anti-inflammation and employed to functionalize selenium nanoparticles (SeNPs), aming to solve of inflammation in UC by accelerating the reprogramming of macrophages. In this study, SeNPs was prepared by selenite and MRO with ascorbic acid reduction. The stability and biocompatibility of SeNPs was obviously improved by the functionalization of MRO, resulting in spheres (2 µM Se) carrying around 26 ng/ml MRO (MRO-SeNPs) with an average diameter of 70 nm remained stable in 60 d. In addition, efficient cellular uptake of MRO-SeNPs in macrophages was detected by contribution of MRO targeted to the receptors of macrophages. As expected, MRO-SeNPs exhibited improvement of macrophage reprogramming in vitro , thus leading to a typical M2 polarization profile of cytokine expression. Furthermore, in DSS-induced mouse colitis model, MRO-SeNPs effectively mitigated colitis by suppressing the pro-inflammatory such as IL-1β, IL-6, TNF-α, IL-12 and MCP-1 cytokines in situ , and exerted salient antioxidant capacity in colon tissues. As a result, MRO-SeNPs exhibited therapeutic potential by promoting macrophages reprogramming leading to inflammation resolution. Taken together, this study not only provides strategy for functionalization of nanomedicines using structure-optimized MRO, but also reveals the action mechanism on successful treatment of IBD and other intestinal diseases. [ABSTRACT FROM AUTHOR]