Nanoparticulate antitumor photodynamic therapy (PDT) has been suffering from the limited dose accumulation in tumor. Herein, we report dually hypoxia- and singlet oxygen-responsive polymeric micelles ...to efficiently utilize the photosensitizer deposited in the disease site and hence facilely improve PDT’s antitumor efficacy. Tailored methoxy poly(ethylene glycol)-azobenzene-poly(aspartic acid) copolymer conjugate with imidazole as the side chains was synthesized. The conjugate micelles (189 ± 19 nm) obtained by self-assembly could efficiently load a model photosensitizer, chlorin e6 (Ce6) with a loading of 4.1 ± 0.5% (w/w). The facilitated cellular uptake of micelles was achieved by the triggered azobenzene collapse that provoked poly(ethylene glycol) shedding; rapid Ce6 release was enabled by imidazole oxidation that induced micelle disassembly. In addition, the singlet oxygen-mediated cargo release not only addressed the limited diffusion range and short half-life of singlet oxygen but also decreased the oxygen level, which could in turn enhance internalization and increase the intracellular Ce6 concentration. The hypoxia-induced dePEGylation and singlet oxygen-triggered Ce6 release was demonstrated both in aqueous buffer and in Lewis lung carcinoma (LLC) cells. The cellular uptake study demonstrated that the dually responsive micelles could deliver significantly more Ce6 to the cells, which resulted in a substantially improved cytotoxicity. This concurred well with the superior in vivo antitumor ability of micelles in a LLC tumor-bearing mouse model. This study presented an intriguing nanoplatform to realize interactively triggered photosensitizer delivery and improved antitumor PDT efficacy.
With the rapid development of materials science, photosensitive materials have been widely used in the field of immunogenic cell death(ICD), which was on account of the reactive oxygen species(ROS) ...generation by photosensitizer under light irradiation inducing cellular oxidative stress during the dying of cells. Considerable researches related to photodynamic therapy(PDT) induced ICD were conducted and exhibited brilliant performance in cancer immunotherapy. Herein, a variety of different strategies for PDT induced ICD have been summarized and discussed to provide researchers more inspiration for cancer immunotherapy.
The non-uniformity of the readout circuit response in the infrared focal plane array unit detector can result in fixed pattern noise with stripe, which seriously affects the quality of the infrared ...images. Considering the problems of existing non-uniformity correction, such as the loss of image detail and edge blurring, a multi-scale residual network with attention mechanism is proposed for single infrared image stripe noise removal. A multi-scale feature representation module is designed to decompose the original image into varying scales to obtain more image information. The product of the direction structure similarity parameter and the Gaussian weighted Mahalanobis distance is used as the similarity metric; a channel spatial attention mechanism based on similarity (CSAS) ensures the extraction of a more discriminative channel and spatial feature. The method is employed to eliminate the stripe noise in the vertical and horizontal directions, respectively, while preserving the edge texture information of the image. The experimental results show that the proposed method outperforms four state-of-the-art methods by a large margin in terms of the qualitative and quantitative assessments. One hundred infrared images with different simulated noise intensities are applied to verify the performance of our method, and the result shows that the average peak signal-to-noise ratio and average structural similarity of the corrected image exceed 40.08 dB and 0.98, respectively.
Resveratrol has been reported to protect several types of cells against β-amyloid peptide (Aβ) toxicity by scavenging reactive oxygen species (ROS) and inactivating caspase-3. However, other studies ...found that long-term treatment with resveratrol inhibited cells by inducing ROS generation and activating caspase-3. In the current report, a 48-h incubation of resveratrol at the concentrations of 5 and 10
μM significantly attenuated the viability of PC12 cells and a 12-h pre-incubation of resveratrol did not protect PC12 cells against Aβ exposure (even further inhibited PC12 cells at the concentrations of 10
μM) by acting as a pro-oxidant. Due to the lipophilicity of resveratrol, resveratrol-loaded polymeric micelles basing on amphiphilic block copolymer were developed. Then, the effects of resveratrol-loaded polymeric micelles on the viability and Aβ protection of PC12 cells were investigated. At the equivalent concentrations of 5 and 10
μM resveratrol, a 48-h incubation of resveratrol-loaded nanoparticles did not show toxicity to cells, while 12-h pre-incubation of resveratrol-loaded nanoparticles protected PC12 cells from Aβ-induced damage in a dose dependent manner (1–10
μM) by attenuating intracellular oxidative stress and caspase-3 activity. Further investigations are absolutely needed to evaluate the feasibility and advantages of in vivo applications of resveratrol-loaded nanoparticles.
Oxidative stress (OS) arises when the body is subjected to harmful endogenous or exogenous factors that overwhelm the antioxidant system. There is increasing evidence that OS is involved in a number ...of diseases, including ovarian cancer (OC). OC is the most lethal gynecological malignancy, and risk factors include genetic factors, age, infertility, nulliparity, microbial infections, obesity, smoking, etc. OS can promote the proliferation, metastasis, and therapy resistance of OC, while high levels of OS have cytotoxic effects and induce apoptosis in OC cells. This review focuses on the relationship between OS and the development of OC from four aspects: genetic alterations, signaling pathways, transcription factors, and the tumor microenvironment. Furthermore, strategies to target aberrant OS in OC are summarized and discussed, with a view to providing new ideas for clinical treatment.
Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine.
...In this study, we established a hybridization capture-based NGS panel including 612 cancer-associated genes, and collected sequencing data of tumors and matched bloods from 153 gastric cancer patients. We performed comprehensive analysis of these sequencing and clinical data.
35 significantly mutated genes were identified such as TP53, AKAP9, DRD2, PTEN, CDH1, LRP2 et al. Among them, 29 genes were novel significantly mutated genes compared with TCGA study. TP53 is the top frequently mutated gene, and tends to mutate in male (p = 0.025) patients and patients whose tumor located in cardia (p = 0.011). High tumor mutation burden (TMB) gathered in TP53 wild-type tumors (p = 0.045). TMB was also significantly associated with DNA damage repair (DDR) genes genotype (p = 0.047), Lauren classification (p = 1.5e-5), differentiation (1.9e-7), and HER2 status (p = 0.023). 38.31% of gastric cancer patients harbored at least one actionable alteration according to OncoKB database.
We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management.
is a dominant halophytic grass in alkalized grasslands of Northeast China. To explore the alkali-tolerance mechanism of
, we applied a widely targeted metabolomic approach to analyze metabolic ...responses of its root exudates, root tissues and leaves under alkali-stress conditions.
extensively secreted organic acids, phenolic acids, free fatty acids and other substances having -COOH or phosphate groups when grown under alkali-stress conditions. The buffering capacity of these secreted substances promoted pH regulation in the rhizosphere during responses to alkali stress.
leaves exhibited enhanced accumulations of free fatty acids, lipids, amino acids, organic acids, phenolic acids and alkaloids, which play important roles in maintaining cell membrane stability, regulating osmotic pressure and providing substrates for the alkali-stress responses of roots. The accumulations of numerous flavonoids, saccharides and alcohols were extensively enhanced in the roots of
, but rarely enhanced in the leaves, under alkali-stress conditions. Enhanced accumulations of flavonoids, saccharides and alcohols increased the removal of reactive oxygen species and alleviated oxygen damage caused by alkali stress. In this study, we revealed the metabolic response mechanisms of
under alkali-stress conditions, emphasizing important roles for the accumulation and secretion of organic acids, amino acids, fatty acids and other substances in alkali tolerance.
Cardiovascular disease is the major cause of death in patients with diabetes. Current treatment strategies for diabetes rely on lifestyle changes and glucose control to prevent angiopathy and organ ...failure. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used as an add-on therapy to insulin treatment. Exenatide also has multiple beneficial effects in addition to its hypoglycemic effects, such as preventing hepatic steatosis and protecting against cardiac injury from doxorubicin-induced cardiotoxicity or ischemic reperfusion. However, the mechanisms underlying the cardioprotective effects of exenatide in diabetes have not been fully clarified. To address this issue, we investigated the cardioprotective effects of exenatide in type 1 and type 2 diabetic mice. We found that exenatide simultaneously attenuated reactive oxidative species (ROS) production through increases in the antioxidant enzymes manganese dependent superoxide dismutase (MnSOD) and catalase. Moreover, exenatide decreased tumor protein P53 (p53) expression and prevented cell apoptosis in H9c2 cells. The presence of the catalase inhibitor 3-AT attenuated the effects of exenatide. Overall, the results strongly indicate that exenatide treatment may be protective against the development of diabetic cardiomyopathy.
Co-delivery of multiple anti-cancer drugs in a single nanoplatform has shown great promise in enhancing therapeutic efficacy and reducing adverse effects. However, the ratiometric dose control is ...pivotal, but often challenging in combinational nanomedicine. Here, we report the employment of cyclodextrin-bearing amphiphilic polymer conjugate micelles for ratiometric, non-covalent loading of three hydrophobic model drugs, curcumin (CUR), camptothecin (CPT), and doxorubicin (DOX) in one single nanocarrier. Each drug was physically encapsulated in the cyclodextrin-bearing polymer conjugate via guest-host complexation. All three drugs displayed a 1:1 complexation behavior with the cyclodextrin, which corresponded to a drug loading of 6.0±0.1% (CUR), 7.5±0.1% (CPT), and 9.0±0.1% (DOX) (w/w). The apparent association constant between the conjugate and drug was 2803.7±87.0 (CUR), 3699.4±123.3 (CPT), and 6760.9±176.3 (DOX), respectively. Ratiometric co-assembly of three types of drug-loaded conjugates produced mixed micelles in a dose- and ratio-controlled manner. The hydrodynamic diameter of co-assembled spherical micelles was ca. 150nm that was similar to the single-drug loaded micelles. The ratiometric co-delivery of three drugs via mixed micelles was demonstrated both in HepG2 cells in vitro and in a mice model in vivo compared to a mixture of free drugs, as evidenced by co-localization analysis. This work provides a facile way to realize ratiometric co-administration of multiple drugs.
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Fluorescent photoswitchable conjugated polymer nanoparticles (PCPNPs) bearing poly(9,9-dihexylfluorene-
alt
-2,1,3-benzoxadiazole) (PFBD) as the fluorescent host polymer and the photochromic ...diarylethene as toggle are synthesized
via
a modified nano-precipitation method using 1,2-distearoyl-
sn
-glycero-3-phosphoethanolamine-
N
-amino(polyethylene glycol)-2000 (DSPE-PEG-NH
2
) as the encapsulation matrix. The PCPNPs are spherical in shape with diameters around 34 nm. The fluorescence switching processes upon UV and white light illumination are successfully demonstrated with high contrast up to 90-fold, recovery efficiency of 95%, and excellent repeatability in solution. The cationic PCPNPs can be easily internalized into cancer cells, and accumulate in tumor tissues, where the fluorescence photoswitching processes can be used to self-validate the imaging results.
Fluorescent photoswitchable conjugated polymer nanoparticles for cell and
ex vivo
tumour imaging with fluorescence on/off contrast over 10-fold in tumour.
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