Abstract Radiofrequency ablation (RFA) is clinically adopted to destruct solid tumors, but is often incapable of completely ablating large tumors and those with multiple metastatic sites. Here we develop a CaCO 3 -assisted double emulsion method to encapsulate lipoxidase and hemin with poly(lactic-co-glycolic acid) (PLGA) to enhance RFA. We show the HLCaP nanoreactors (NRs) with pH-dependent catalytic capacity can continuously produce cytotoxic lipid radicals via the lipid peroxidation chain reaction using cancer cell debris as the fuel. Upon being fixed inside the residual tumors post RFA, HLCaP NRs exhibit a suppression effect on residual tumors in mice and rabbits by triggering ferroptosis. Moreover, treatment with HLCaP NRs post RFA can prime antitumor immunity to effectively suppress the growth of both residual and metastatic tumors, also in combination with immune checkpoint blockade. This work highlights that tumor-debris-fueled nanoreactors can benefit RFA by inhibiting tumor recurrence and preventing tumor metastasis.
Sonodynamic therapy (SDT), a noninvasive and highly penetrating tumor therapy, which employs ultrasound and sonosensitizers, has attracted extensive attention because of its ability to treat deep tumors. However, many current sonosensitizers have drawbacks in phototoxicity and limited sonodynamic effect. Herein, as a novel kind of sonosensitizer, iron-doped vanadium disulfide nanosheets (Fe-VS2 NSs) are constructed by a high-temperature organic-solution method and further modified with polyethylene glycol (PEG). With Fe doping, the sonodynamic effect of Fe-VS2 NSs is greatly enhanced, owing to the prolonged electron–hole recombination time. Simultaneously, such Fe-VS2-PEG NSs as a good Fenton agent can be utilized for chemodynamic therapy (CDT) by using the endogenous H2O2 in the tumor microenvironment (TME). Moreover, the multivalent Fe and V elements in the Fe-VS2 NSs can consume glutathione to amplify the reactive oxygen species-induced oxidative stress by SDT and CDT. Utilizing the strong near-infrared optical absorbance and enhanced magnetic resonance (MR) contrast by Fe-VS2 NSs, photoacoustic/MR biomodal imaging reveals a high accumulation of Fe-VS2-PEG NSs in the tumor. The great tumor suppression effect is then achieved by the in vivo combined CDT&SDT treatment. Importantly, most of the injected Fe-VS2-PEG NSs can be gradually decomposed and excreted from the mice, making them as safe sonosensitizers for cancer treatment. Our work highlights a new type of biodegradable sonosensitizer with the ability of regulating TME for applications in cancer theranostics.
Nanotechnology-mediated anti-inflammatory therapy is emerging as a novel strategy for the treatment of inflammation-induced injury. However, one of the main hurdles for these anti-inflammatory nano-drugs is their potential toxic side effects in vivo. Herein, we uncovered that polydopamine (PDA) nanoparticles with their structure and chemical properties similar to melanin, a natural bio-polymer, displayed a significant anti-inflammation therapeutic effect on acute inflammation-induced injury. PDA with enriched phenol groups functioned as a radical scavenger to eliminate reactive oxygen species (ROS) generated during inflammatory responses. As revealed by in vivo photoacoustic imaging with a H2O2-specific nanoprobe, PDA nanoparticles remarkably reduced intracellular ROS levels in murine macrophages challenged with either H2O2 or lipopolysaccharide (LPS). The anti-inflammatory capacity of PDA nanoparticles was further demonstrated in murine models of both acute peritonitis and acute lung injury (ALI), where diminished ROS generation, reduced proinflammatory cytokines, attenuated neutrophil infiltration, and alleviated lung tissue damage were observed in PDA-treated mice after a single dose of PDA treatment. Our work therefore presents the great promise of PDA nanoparticles as a biocompatible nano-drug for anti-inflammation therapy to treat acute inflammation-induced injury.
Female sports education is an indispensible part of higher-educational system,and also a weaker part.Through documentary review,statistical investigation and other methods,this essay makes an exploration on some common problems which restrict university education,female social virtues,physiological and psychological characterestics,physical ceducation and outdoor activities.It also raises that it is necessary to strengthen the tempering of female's sports morality will and moral behavior.
This study aims to explore the high-risk factors of carbapenem-resistant Enterobacteriaceae (CRE) infection of hospitalised patients in high-risk departments. This study is a multicentre, retrospective study. CRE screening positive patients from 1 January 2016 to 31 December 2018 of high-risk departments in five tertiary first-class teaching hospitals in Beijing collect the patients' CRE test specimen information, CRE infection information and outcomes. The patients were divided into a colonisation group and an infection group for comparative analysis. A logistic regression model was established to explore the risk factors of CRE infection. Subgroup analysis was conducted according to invasive procedures and the type of the infection. In total, 344 patients were included in this study, including 85 (24.71%) colonisation and 259 (75.29%) infection; 36.09% CRE colonisation converted to infection, and the mean conversion time from colonisation to infection was 6.5 (4.0, 18.8) days. Renal disease, granulocytosis, invasive procedures and the time from hospital stay to positive CRE were the risk factors for CRE infection. The subgroup analysis showed that the rate of CRE infection in the invasive group was higher than in the non-invasive group (P < 0.001), and the rate of exacerbation or death in the invasive group was also higher than in the non-invasive group (P = 0.019). The average length of ICU and hospitalisation in the healthcare-associated infection group were significantly higher than those in the community infection group, but there was no difference in the proportion of final exacerbation or death between them (P = 0.727). Kidney disease, granulocytosis, invasive procedures and CRE detection time are the risk factors for CRE infection. Carrying out CRE screening in patients as early as possible and taking effective intervention measures in time to avoid adverse consequences is all important.
Upconversion nanoparticles (UCNPs), particularly lanthanide-doped nanocrystals, which emit high energy photons under excitation by the near-infrared (NIR) light, have found potential applications in many different fields, including biomedicine. Compared with traditional down-conversion fluorescence imaging, the NIR light excited upconversion luminescence (UCL) imaging relying on UCNPs exhibits improved tissue penetration depth, higher photochemical stability, and is free of auto-fluorescence background, which promises biomedical imaging with high sensitivity. On the other hand, the unique upconversion process of UCNPs may be utilized to activate photosensitive therapeutic agents for applications in cancer treatment. Moreover, the integration of UCNPs with other functional nanostructures could result in the obtained nanocomposites having highly enriched functionalities, useful in imaging-guided cancer therapies. This review article will focus on the biomedical imaging and cancer therapy applications of UCNPs and their nanocomposites, and discuss recent advances and future prospects in this emerging field.
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