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•CaCO3 capped mesoporous silica nanoparticles with surface camouflaged with cancer cell membrane.•The nanoparticles is constructed only by naturally biomaterials.•The nanoparticles ...combine biocompatibility, pH-sensitive drug release and homotypic targeting.•The nanoparticles efficiently inhibited prostate tumor growth.
Nanoparticular drug delivery system (NDDS) has great potential for enhancing the efficacy of traditional chemotherapeutic drugs. However, it is still a great challenge to fabricate a biocompatible NDDS with simple structure capable of optimizing therapeutic efficacy, such as high tumor accumulation, suitable drug release profile (e.g. no premature drug leakage in normal physiological conditions while having a rapid release in cancer cells), low immunogenicity, as well as good biocompatibility. In this work, a simple core/shell structured nanoparticle was fabricated for prostate cancer treatment, in which a mesoporous silica nanoparticle core was applied as a container to high-efficiently encapsulate drugs (doxorubicin, DOX), CaCO3 interlayer was designed to act as sheddable pH-sensitive gatekeepers for controlling drug release, and cancer cell membrane wrapped outlayer could improve the colloid stability and tumor accumulation capacity. In vitro cell experiments demonstrated that the as-prepared nanovehicles (denoted as DOX/MSN@CaCO3@CM) could be efficiently uptaken by LNCaP-AI prostate cancer cells and even exhibited a better anti-tumor efficiency than free DOX. In addition, Live/Dead cell detection and apoptosis experiment demonstrated that MSN/DOX@CaCO3@CM could effectively induce apoptosis-related death in prostate cancer cells. In vivo antitumor results demonstrated that DOX/MSN@CaCO3@CM administration could remarkably suppress the tumor growth. Compared with other tedious approaches to optimize the therapeutic efficacy, this study provides an effective drug targeting system only using naturally biomaterials for the treatment of prostate cancer, which might have great potential in clinic usage.
Catalytic anticancer metallodrugs active at low doses could minimize side-effects, introduce novel mechanisms of action that combat resistance and widen the spectrum of anticancer-drug activity. Here ...we use highly stable chiral half-sandwich organometallic Os(II) arene sulfonyl diamine complexes, Os(arene)(TsDPEN) (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), to achieve a highly enantioselective reduction of pyruvate, a key intermediate in metabolic pathways. Reduction is shown both in aqueous model systems and in human cancer cells, with non-toxic concentrations of sodium formate used as a hydride source. The catalytic mechanism generates selectivity towards ovarian cancer cells versus non-cancerous fibroblasts (both ovarian and lung), which are commonly used as models of healthy proliferating cells. The formate precursor N-formylmethionine was explored as an alternative to formate in PC3 prostate cancer cells, which are known to overexpress a deformylase enzyme. Transfer-hydrogenation catalysts that generate reductive stress in cancer cells offer a new approach to cancer therapy.
The relationship between metformin and prostate cancer (PCa) remains controversial. To clarify this association, the PubMed, Embase and Cochrane library databases were systematically searched from ...their inception dates to May 23, 2018, using the keywords "metformin" and "prostate cancer" to identify the related studies. The results included incidence, overall survival (OS), PCa-specific survival (CSS) and recurrence-free survival (RFS), which were measured as hazard ratios (HR) with a 95% confidence interval (95% CI) using Review Manager 5.3 software. A total of 30 cohort studies, including 1,660,795 patients were included in this study. Our study revealed that metformin treatment improves OS, CSS and RFS in PCa (HR = 0.72, 95% CI: 0.59-0.88, P = 0.001; HR = 0.78, 95% CI: 0.64-0.94, P = 0.009; and HR = 0.60, 95% CI: 0.42-0.87 P = 0.006, respectively) compared with non-metformin treatment. However, metformin usage did not reduce the incidence of PCa (HR = 0.86, 95% CI: 0.55-1.34, P = 0.51). In conclusion, compared with non-metformin treatment, metformin therapy can significantly improve OS, CSS and RFS in PCa patients. No association was noted between metformin therapy and PCa incidence. This study indicates a useful direction for the clinical treatment of PCa.
Most cancer diagnoses rely on biomarkers detection. This could be improved if directly conducted in suspicious cancer spots, preventing the need for biopsy. Lung cancer remains a perfect study-case ...for such a development, as it is generally detected at advanced stage and is in the need for early diagnosis techniques. To this aim, we have designed a minimally invasive catheter-embedded biosensor. It combines a specific grating structure photo-imprinted in a telecommunication-grade optical fiber and an overlay made of a thin metal coating on which receptors are grafted, yielding plasmonic coupling. Our optrode targets a type of cytokeratins, overexpressed at the surface of cancer cells. It was assayed ex vivo in resected lung tissues collected from a dozen of patients. Biosensing responses were confirmed by immunohistochemistry, conducted on the same samples. In addition to accurate biosensing, our gratings inherently enable force-sensing features, which also allow a fine positioning of the probe in the tissue. Finally, the in vivo navigation of the bronchoscope-embedded sensor was validated into pig lungs. These achievements are a critical milestone towards the development of this micro/nano biosensor as a cost-effective and weakly invasive diagnostic tool for applications in areas of critical access such as brain, liver or prostate.
•Minimally-invasive catheter-embedded optrodes.•Cancer biomarker detection in resected human lung tissues.•In vivo plasmonics in pig lungs.•Optical fiber biosensor enabling force sensing features for finely controlled probe positioning.
Prostate specific antigen (PSA) is a widely used marker for the diagnosis of prostate cancer, and the increasing attention has been attracted on the development of rapid assay using biosensing ...technology. However, it remains challenging for the sensitive and selective detection of PSA in clinical samples. Here, we report a label-free microfluidic paper-based analytical device for highly sensitive electrochemical detection of PSA. The paper device was fabricated with wax printing to generate hydrophobic and hydrophilic layers for the construction of microfluidic channel, followed by screen-printing of three electrodes including working, counter and reference electrode. Gold nanoparticles (AuNPs)/reduced graphene oxide (rGO)/thionine (THI) nano composites were synthesized and characterized, which were coated onto working electrodes for the immobilization of DNA aptamer probe. THI servers as the electrochemical mediator to transduce the biological recognition between DNA aptamer and PSA, and the excellent conductivity of AuNPs and rGO also play a significant role of electron transfer, leading to a sensitive detection for PSA, able to detect PSA as low as 10 pg mL−1, with a linear range from 0.05 to 200 ng mL−1. We demonstrated that our electrochemical sensor for the detection of clinical serum samples, indicating that our sensor would provide a new platform for low cost, sensitive and point-of-care diagnosis of prostate cancer.
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•A low-cost paper-based aptasensor was developed for the sensitive and selective detection of prostate specific antigen.•A novel hybridized nanomaterial was synthesized to improve the analytical performance of aptasensors.•The aptasensor is able to detect the cancer biomarker in the clinical serum.
Purpose
We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific ...membrane antigen (LuPSMA) phase 2 trial.
Methods
PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment.
Results
This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4–4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8–0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2–4.4), ALP (HR 1.1; 95% CI, 1–1.2) and LDH (HR 1.2; 95% CI, 1–1.5) as biomarkers prognostic of overall survival.
Conclusions
In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.
Ancestral environmental exposures to a variety of factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. One of the most widely used ...agricultural pesticides worldwide is the herbicide glyphosate (N-(phosphonomethyl)glycine), commonly known as Roundup. There are an increasing number of conflicting reports regarding the direct exposure toxicity (risk) of glyphosate, but no rigorous investigations on the generational actions. The current study using a transient exposure of gestating F0 generation female rats found negligible impacts of glyphosate on the directly exposed F0 generation, or F1 generation offspring pathology. In contrast, dramatic increases in pathologies in the F2 generation grand-offspring, and F3 transgenerational great-grand-offspring were observed. The transgenerational pathologies observed include prostate disease, obesity, kidney disease, ovarian disease, and parturition (birth) abnormalities. Epigenetic analysis of the F1, F2 and F3 generation sperm identified differential DNA methylation regions (DMRs). A number of DMR associated genes were identified and previously shown to be involved in pathologies. Therefore, we propose glyphosate can induce the transgenerational inheritance of disease and germline (e.g. sperm) epimutations. Observations suggest the generational toxicology of glyphosate needs to be considered in the disease etiology of future generations.
Simultaneous detection of free and complexed prostate-specific antigen (f-PSA and c-PSA) is critical to the prostate cancer (PCa) diagnostic accuracy for clinical samples with PSA values in the ...diagnostic gray zone between 4 and 10 ng mL−1. Herein, red and green magnetic-quantum dot nanobeads (MQBs) with superior magnetic property and high luminescence were fabricated via polyethyleneimine-mediated electrostatic adsorption of numerous quantum dots onto superparamagnetic Fe3O4 magnetic cores, and were conjugated with f-PSA antibody and c-PSA antibody, respectively, as versatile fluorescent probes in test strip for immune recognition, magnetic enrichment, and simultaneous detection of f-PSA and c-PSA analytes in complex biological matrix with t-PSA antibody on the test line. A low-cost and portable smartphone readout device with an application was also developed for the imaging of dual-color test strips and data processing. This assay can simultaneously detect f-PSA and c-PSA with the limits of detection of 0.009 ng mL−1 and 0.087 ng mL−1, respectively. Clinical serum samples of PCa and benign prostatic hyperplasia patients were evaluated to confirm the clinical feasibility. The results suggest that the proposed dual-color MQBs-based fluorescent lateral flow immunoassay is a promising point-of-care diagnostics technique for the accurate diagnosis of PCa even in resource-limited settings.
•Dual-color magnetic-quantum dot nanobeads (MQBs) with superior magnetic property and high luminescence are fabricated.•Red and green MQBs are conjugated with f-PSA antibody and c-PSA antibody, respectively, as versatile fluorescent probes.•Immune recognition, magnetic enrichment, and simultaneous detection of f-PSA and c-PSA analytes in complex clinical samples.•High-sensitive detection of f-PSA and c-PSA with LODs of 0.009 ng mL−1 and 0.087 ng mL−1, respectively.
The site‐selective C−H amination reaction of 7‐azaindoles with various benzisoxazoles as amination surrogates under cationic rhodium(III) catalysis is described. This transformation efficiently ...provides a range of ortho‐aminated N‐aryl‐7‐azaindoles with excellent site‐selectivity and functional group compatibility. The formed ortho‐aminated 7‐azaindoles were readily transformed into biologically relevant heterocycles such as azaindoloacridine, azaindoloacridone, and bis‐indole compounds. Moreover, the synthetic derivatives were tested for in vitro anticancer activity against human breast adenocarcinoma cells (MCF‐7), human renal carcinoma cells (786‐O), and human prostate adenocarcinoma cells (DU145). Notably, some synthetic compounds were found to display most potent anticancer activity, compared to that of anticancer doxorubicin as a positive control.
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