Highly Active Coreactant-Capped and Water-Stable 3D@2D Core-Shell Perovskite Quantum Dots as a Novel and Strong Self-Enhanced Electrochemiluminescence Probe.

Self-enhanced electrochemiluminescence (ECL) probes have attracted more and more attention in analytical chemistry for their significant simplification of the ECL sensing operation while improving the ECL sensing sensitivity. However, the development and applications of self-enhanced ECL probes are still in their infancy and mainly suffer from the requirement of a complicated synthesis strategy and relatively low self-enhanced ECL activity. In this work, we took advantage of the recently emerged perovskite quantum dots (PQDs) with high optical quantum yields and easy surface engineering to develop a new type of PQD-based self-enhanced ECL system. The long alkyl chain (C18) diethanolamine (i.e., N-octadecyldiethanolamine (ODA)) with high ECL coreactant activity was selected as a capping ligand to synthesize an ODA-capped PQD self-enhanced ECL probe. The preparation of the coreactant-capped PQDs is as simple as for the ordinary oleylamine (OAm)-capped PQDs, and the obtained ODA-capped PQDs exhibit very strong self-enhanced ECL activity, 82.5 times higher than that of traditional OAm-capped PQDs. Furthermore, the prepared ODA-PQDs have a unique nanostructure (ODA-CsPbBr3@CsPb2Br5), with the highly emissive 3D CsPbBr3 PQD as the core and the water-stable 2D CsPb2Br5 as the shell, which allows ODA-PQDs to be very stable in aqueous media. It is envisioned that the prepared ODA-3D@2D PQDs with the easy preparation method, strong self-enhanced ECL, and excellent water stability have promising applications in ECL sensing.

Photochromic Perovskite Nanocrystals for Ultraviolet Dosimetry.

Excessive ultraviolet (UV) radiation has serious damage to human's health, therefore the development of visible, portable, and wearable sensor for monitoring UV radiation, especially the cumulative UV dosage, is highly desired but full of challenges. Herein, a wearable and flexible UV dosimeter based on photochromic perovskite nanocrystals (PNCs) is designed. The obtained CsPbCl3 PNCs dispersed in dibromomethane (PNCs-DBM) undergo continuous, vivid, and multiple (from very weak purple to blue, cyan, and finally strong green) color change in response to UV radiation. It is demonstrated that the UV-induced degradation of DBM and subsequent anion-exchange reaction between CsPbCl3 and Br-, play a crucial role in the color change of PNCs-DBM. The properties of continuous fluorescence color change and enhanced fluorescence intensity enable the construction of sensitive and visible UV dosimeter. Furthermore, by integrated photochromic PNCs with flexible bracelet or PDMS substrate, a wearable UV sensor or a multi-indicator array for the detection of solar UV dosage is developed. This work may advance the fundamental understanding about photochromic perovskite, and show promising application of perovskite nanomaterials in easily fabricated, low-cost, visualized, and wearable solar UV dosimeter.

Ubiquitylation of RUNX3 by RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, but the early diagnosis rate is low. The RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in several cancers but its mechanism of action in LUAD is unclear. In this study, the biological activity of MEX3C was assessed in LUAD. MEX3C and RUNX3 mRNA levels in the tissues of LUAD patients were determined using reverse transcription­quantitative PCR. The involvement of MEX3C in the growth and metastasis of LUAD cells was measured by EdU assay, CCK-8, colony formation, Transwell assay, TUNEL, and flow cytometry. Expression of apoptosis and epithelial-mesenchymal transition related proteins were determined using western blotting analysis. LUAD cells transfected with si-MEX3C were administered to mice subcutaneously to monitor tumor progression and metastasis. We found that MEX3C is strongly upregulated in LUAD tissue sections, and involved in proliferation and migration. A549 and H1299 cells had significantly higher levels of MEX3C expression compared to control HBE cells. Knockdown of MEX3C dramatically decreased cell proliferation, migration, and invasion, and accelerated apoptosis. Mechanistically, we demonstrate MEX3C induces ubiquitylation and degradation of tumor suppressor RUNX3. Moreover, RUNX3 transcriptionally represses Suv39H1, as revealed by RNA pull-down and chromatin immunoprecipitation assays. The in vivo mice model demonstrated that knockdown of MEX3C reduced LUAD growth and metastasis significantly. Collectively, we reveal a novel MEX3C-RUNX3-Suv39H1 signaling axis driving LUAD pathogenesis. Targeting MEX3C may represent a promising therapeutic strategy against LUAD.

Facile Synthesis of Oxidized Boron Nanosheets for Chemo- and Biosensing.

As recently emerging nanomaterials, boron nanosheets (BNSs) have attracted more and more attention in various fields such as supercapacitors, photodetectors, bioimaging, and electrocatalysis due to their advantages of good biological compatibility, environmental friendliness, and good electro-optical properties. However, the study and application of BNSs in chemical and biological sensing are still in the infant stage, mainly due to the requirement of complicated, high-cost, and time-consuming preparation strategies. In this work, a new class of BNSs, namely oxidized-BNSs (i.e., ox-BNSs), were easily and rapidly synthesized by chemically treating boron powder with diluted HNO3 in a very short time (less than 15 min). The composition, morphology, optical property, and peroxidase mimetic activity of obtained ox-BNSs were investigated in detail. The prepared ox-BNSs were several-layered nanosheets with abundant oxygen-containing groups, emitted blue fluorescence, and possessed good intrinsic peroxidase mimetic activity, based on which a sensitive and selective colorimetric sensor was developed for detection of H2O2 and glucose. The new easy preparation strategy and good sensing performances of the prepared ox-BNSs would greatly stimulate the study and application of BNSs in chemo- and biosensing.

Anion Exchanges of Water-Stable Perovskite Nanocrystals in the Pure Water Phase and Applications in Detecting Halide Ions via a Smartphone-Based Sensing Platform.

Recently, the newly emerging lead halide perovskite nanocrystals (PNCs) have been intensely researched in many fields, such as light-emitting diodes (LEDs), solar cells, lasers, and display devices. The extremely high fluorescence quantum yield (near 100%) of PNCs over classic fluorescent materials would enable good applications of PNCs in sensing. However, the study on PNCs for bio- and chemical sensing, especially for detecting targets that exist in aqueous medium, faces great challenges due to the well-known instability of PNCs in polar solvents, especially water. Although the encapsulation of polymers or inorganic materials can efficiently protect PNCs from decomposition in aqueous solution, the sensing based on the interaction between PNCs and targets is severely hindered by the compact protection coating at the surfaces of PNCs. In this work, novel water-dispersed PNCs (W-PNCs), i.e., CsPbBr3@CsPb2Br5 PNCs, with strong fluorescence and excellent water stability were synthesized from OAm-capped CsPbBr3 PNCs by a simple "oil-solid-water" phase transition. The W-PNCs without being encapsulated with compact polymers or inorganic materials can sensitively and stably sense targets in the pure water phase via direct chemical reactions. For the first time, ion exchanges between PNCs and halide ions and their effects on the fluorescence wavelength of PNCs were investigated in the pure water phase, on the basis of which a new, visualized, selective, and sensitive smartphone-based sensing platform for halide ions has been established by the integration of the conveniently prepared W-PNC nanoprobe and the portable mobile phone. It is envisioned that the uncoated but extremely water-stable and highly fluorescent W-PNCs have promising applications in chemical sensing, biosensing, and bioimaging of targets in aqueous medium.

Hydrochromic Perovskite System with Reversible Blue-Green Color for Advanced Anti-Counterfeiting.

The intrinsic instability of halide perovskites toward to external stimulus, has created a competitive advantage for designing stimuli-responsive materials. However, the external environment tuning reversibly fluorescence emission of perovskite system is still limited. In this work, humidity is verified to act as a new option to modulate the emission properties of mixed-halide perovskite. The perovskite nanocrystals (PNCs) photoirradiated in dichloromethane are easily and stably redispersed in water, and emit bright fluorescence which is quite different from the original. Moreover, the perovskites confined on glass slide can reversibly switch their fluorescence between blue and green colors under moisture. It is demonstrated that the factors of different solubilities of CsCl and CsBr in water, the structural transformation of perovskites and the confine of glass matrix play key roles in the reversible transformation. Finally, the combination of hydrochromic CsPb(Brx Cly )3 and water-resistant CsPb(Brx Cly )3 -polymethyl methacrylate have been applied in advanced anti-counterfeiting, which greatly improves the information security. This work not only give an insight into the effects of humidity on fluorescence and structures of PNCs, but also offer a new class of hydrochromic PNCs materials based on reversible emission transformation for potential application in sensors, anti-counterfeiting and information encryption.

1-Monopalmitin promotes lung cancer cells apoptosis through PI3K/Akt pathway in vitro.

Lung cancer is the leading cause of cancer-related death worldwide and non-small cell lung cancer (NSCLC) represents 85%. Mougeotia nummuloides and Spirulina major have been reported to possess anticancer properties. 1-Monopalmitin (1-Mono) is the principle active constituent in these natural plants. It is debating whether 1-Mono exerts antitumor effects. Therefore, we explored the role of 1-Mono in lung cancer in vitro. Results showed that 1-Mono significantly inhibited A549 and SPC-A1 cell proliferation, induced G2/M arrest and caspase-dependent apoptosis. Moreover, it suppressed the protein expression of inhibitors of apoptosis proteins (IAPs). It was further demonstrated that 1-Mono activated the PI3K/Akt pathway, suppression of PI3K/Akt activities with LY294002 and Wortmannin partially attenuated 1-Mono-mediated anticancer activities, indicating that 1-Mono-induced antitumor effects is dependent on PI3K/Akt pathway. 1-Mono induced cytoprotective autophagy since autophagy inhibitor Chloroquine dramatically enhanced 1-Mono-induced cytotoxicity. In summary, our results showed 1-Mono kills lung cancer through PI3K/Akt pathway, providing novel options for lung cancer administration.

Highly Electrochemiluminescent Cs4PbBr6@CsPbBr3 Perovskite Nanoacanthospheres and Their Application for Sensing Bisphenol A.

Perovskite quantum dots (PQDs) as recently emerging electrochemiluminescence (ECL) luminophores have been paid much attention due to their good ECL activity, narrow ECL spectra, and easy preparation. However, the PQDs used for ECL sensing were mainly inherited from those PQDs prepared as strong fluorescence (FL) luminophores, which would limit the finding of highly ECL PQDs for sensing due to the very different mechanisms in generating excited-state luminophores between ECL and FL. In order to obtain highly electrochemiluminescent PQDs, for the first time we proposed to synthesize PQDs for ECL sensing rather than for FL-based analysis by optimizing the synthesis conditions. It was revealed that the volume of the precursor solution, the concentrations of CsBr and PbBr2, the amount of capping reagents, and the synthesis reaction temperature all significantly affect the ECL activity of PQDs. On the basis of the optimization of the synthesis conditions, we obtained a new type of PQDs with high ECL activity. The new PQDs were characterized by several technologies, such as scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and energy dispersive X-ray spectrum, to be the hybrids of 3D PQDs (CsPbBr3) and 0D PQDs (Cs4PbBr6) with unique morphologies, i.e., Cs4PbBr6@CsPbBr3 PQD nanoacanthospheres (PNAs), in which Cs4PbBr6 was as the core and CsPbBr3 served as the shell. The obtained Cs4PbBr6@CsPbBr3 PNAs had much higher (>4 times) ECL activity than the prevailing 3D (CsPbBr3) PQDs. Finally, the novel Cs4PbBr6@CsPbBr3 PNAs have been applied for the ECL sensing of bisphenol A (BPA), showing a promising application of the highly electrochemiluminescent PQDs in analytical chemistry.

Effects of C-Related Dangling Bonds and Functional Groups on the Fluorescent and Electrochemiluminescent Properties of Carbon-Based Dots.

Single-layer carbon-based dots (SCDs) were chosen as a model to investigate the effect of the C-related dangling bonds with spin S=1/2 and functional groups on the electrochemiluminescent (ECL) and fluorescent (FL) properties of CDs. The C-related dangling bonds and functional groups of SCDs were tuned by chemical reduction with NaBH4 . There have several main findings via investigating the ECL and FL properties of SCDs before and after the chemical reduction. First, the FL and ECL of CDs are highly dependent on their concentration, and luminescent resonance energy transfer is observed in ECL studies when the concentration of CDs is high. Second, the ECL activity of CDs is greatly enhanced as the C-related dangling bonds increase, proving that the ECL of CDs originates from the C-related dangling bonds. Third, the FL of CDs is the synthesis of the inner FL originated from the contained isolated sp2 units and the defect FL from the C-related dangling bonds. The inner FL of CDs is enhanced greatly by removing the carboxyl groups, while the defect FL is increased slightly due to the increased C-related dangling bonds. We believe this study would promote our understanding in the ECL and FL mechanisms of CDs, advancing the applications of CDs based on their ECL and FL properties.

Combined analysis of pri-miR-34b/c rs4938723 and TP53 Arg72Pro with cervical cancer risk.

miR-34 family members can form a p53-miR-34 positive feedback loop and induce apoptosis, DNA repair, angiogenesis, and cell cycle arrest. We conducted a case-control study to examine whether two polymorphisms (i.e., rs4938723 in the promoter of pri-miR-34b/c and TP53 Arg72Pro) were linked to the carcinogenesis of cervical cancer among Chinese Han women. Genotypes of the two polymorphisms in 328 cervical cancer patients and 568 control subjects were determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. We found a significantly increased cervical cancer risk in the pri-miR-34b/c rs4938723 under dominant and overdominant model (CT/CC vs. TT: adjusted OR = 1.34, 95 % CI = 1.01-1.77; CT vs. TT/CC: adjusted OR = 1.37, 95 % CI = 1.05-1.80, respectively). Increased cervical cancer risks were also found in the TP53 Arg72Pro under a heterozygous comparison and overdominant model (CG vs. GG: adjusted OR = 1.44, 95 % CI = 1.06-1.95; CG vs. GG/CC: adjusted OR = 1.47, 95 % CI = 1.12-1.94, respectively). Stratification analysis showed that patients carrying the pri-miR-34b/c rs4938723 CT genotype had a significantly increased risk for developing poorly differential status and clinical stage I. Moreover, increased cancer risks were observed for the TP53 Arg72Pro polymorphism in patients with poorly differential status, clinical stage II, and without lymph node metastasis. Combined analysis revealed that the genotypes of rs4938723 CT/CC and TP53 Arg72Pro CG/CC had an increased cervical cancer risk (OR = 2.21, 95 % CI = 1.38-3.53). These findings suggest that the pri-miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms may contribute to the genesis of cervical cancer.

Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk of gastric cancer.

A long ncRNA (lncRNA) prostate cancer non-coding RNA 1 (PRNCR1) in the 8q24 has been reported to be upregulated in prostate cancer with a function of activating androgen receptor (AR). AR plays a key role in the gender disparity, cell migration, and invasion of gastric cancer (GC). We hypothesized that single nucleotide polymorphisms (SNPs) in the lncRNA PRNCR1 may be related to the risk of GC. We conducted a case-control study to investigate the association between SNPs in the lncRNA PRNCR1 and the risk of GC. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to determine the genotypes of 613 subjects including 219 cases with GC and 394 controls. We found that patients with the rs13252298AG genotype displayed a 1.50-fold increased risk of GC (AG vs. AA, 95 % confidence interval (CI) = 1.05-2.12, p = 0.02). Interestingly, the rs7007694CT and CC and the rs1456315GG genotypes displayed a decreased risk of GC (rs7007694CT vs. TT, odds ratio (OR) = 0.68, 95 % CI = 0.48-0.97, p = 0.03; rs7007694CC vs. TT, OR = 0.36, 95 % CI = 0.13-0.97, p = 0.04; rs1456315GG vs. AA, OR = 0.30, 95 % CI = 0.13-0.70, p = 0.004, respectively). Our results suggest that SNPs in the lncRNA PRNCR1 may be a biomarker for the etiology of GC.

Interaction analysis of IL-12A and IL-12B polymorphisms with the risk of colorectal cancer.

IL-12 is an antitumor cytokine with functions of inhibiting tumor growth, invasion, and metastasis, indicating that IL-12 is a promising candidate for cancer treatment. The aim of this study was to investigate the association of IL-12A rs568408, IL-12A rs2243115, and IL-12B rs3212227 with the susceptibility to colorectal cancer (CRC). Two hundred and fifty-seven histopathologically confirmed CRC patients and 236 age- and gender-matched controls were enrolled. The three polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. We found that the IL-12A rs568408 AG/AA genotypes were associated with an increased risk of CRC with an adjusted odds ratio (OR) of 1.66 (95 % confidence interval (CI), 1.11-2.48). Stratified analyses showed that patients carrying the IL-12B rs3212227AC/CC genotypes had a 1.97-fold increased risk of tumor metastasis (OR = 1.97; 95 % CI, 1.04-3.70). Gene-gene interaction analysis showed that subjects carrying the IL-12A rs568408AG/AA and IL-12B rs3212227AA genotypes had a 2.40-fold increased risk of CRC (OR = 2.40; 95 % CI, 1.14-5.07) and individuals carrying the IL-12A rs568408AG/AA and IL-12B rs3212227AC/CC genotypes had a 1.93-fold increased risk of CRC (OR = 1.93; 95 % CI, 1.10-3.41). These findings indicate that IL-12A rs568408 and IL-12B rs3212227 may be related to the development of CRC.

A let-7 KRAS rs712 polymorphism increases colorectal cancer risk.

Growing evidence has indicated that polymorphism present in the miRNA binding site of target gene can alter the ability of miRNAs to bind its target gene and modulate the development and progression of cancer. We aimed to investigate the association between let-7 KRAS rs712 polymorphism and the risk of colorectal cancer (CRC). The let-7 KRAS rs712 was analyzed in a case-control study, including 339 CRC patients and 313 age- and sex-matched controls; the relationship between the polymorphism and the clinicopathological features of CRC was also examined. Individuals carrying the let-7 KRAS rs712 TT genotype and T allele had an increased risk of developing CRC (TT vs. GG, adjusted OR = 2.18; 95% CI, 1.00-4.77; T vs. G, adjusted OR = 1.50; 95% CI, 1.15-1.96). Stratified analyses revealed that CRC patients with the let-7 KRAS rs712 TT genotype were more likely to have clinical stage III or IV disease (OR = 3.29, 95% CI, 1.32-8.20) and distant metastasis (OR = 4.70, 95% CI, 1.81-12.25). These findings provide evidence that the let-7 KRAS rs712 polymorphism may play crucial roles in the etiology of CRC.

Ligand-free Pd-catalyzed highly selective arylation of activated and unactivated alkenes via oxidative and reductive heck coupling.

In this work, an eco-friendly, green, efficient approach for oxidative and reductive Heck-Mizoroki (HM) reactions was developed, which offered acceptable yields from first-pass experiments. Mono-arylation was achieved without the use of ligands, directing groups, or prefunctionalized alkenes. Considering mild reaction conditions, good functional group compatibility, and great regioselectivity, the method can find broad applications in novel medicine and material development and discovery processes.

Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is a disease in which long-term use of glucocorticoid causes bone loss, deterioration of bone microstructure and fracture. Currently, clinical drugs targeting this disease have certain side effects. There is still a need to find effective drugs with fewer side effects. The theory of traditional Chinese medicine suggests that YGJ has therapeutic effect on GIOP, but it has not been explained. Therefore, this study aims to explore the protective effect of YGJ on GIOP mouse models and elucidate the underlying mechanism through LC-MS-based metabolomics analysis. METHODS: The general condition of 8 week age male C57BL/6J mice was recorded after 8 weeks of treatment with dexamethasone (DEX) and YGJ. Bone-related parameters and bone morphology were determined by Micro-CT. HE staining was used to observe the pathological changes of bone tissue. Serum levels of bone metabolism markers were detected by ELISA. Liver metabolomics analysis was conducted to search for the significant markers of anti-GIOP of YGJ and the metabolic pathway affecting it. RESULTS: After treatment, YGJ significantly reversed the weight loss caused by DEX; increase the number of bone trabecular in ROI region, significantly improve the bone-related parameters of GIOP mice, and increase the levels of alkaline phosphatase and osteocalcin. In the study of metabolic mechanism, YGJ reversed 24 potential markers in GIOP mice. These included cortisol, 3-hydroxybutyric acid, taurine, esculin and uric acid, which are closely associated with osteoporosis. Topological analysis results showed that YGJ had the most significant effect on taurine and hypotaurine metabolism, with - log10 (P) > 2.0 and Impact > 0.4. CONCLUSIONS: Yi-Guan-Jian decoction can increase bone density and improve bone microstructure by regulating the levels of alkaline phosphatase and osteocalcin and reverse bone loss in GIOP mouse model. The underlying metabolic mechanism may be related to taurine and hypotaurine metabolic pathway.

Transient directing group enabled Pd-catalyzed C-H oxygenation of benzaldehydes and benzylic amines.

We report a general protocol for ortho-C-H fluoroalkoxylation of benzaldehydes and benzylic amines utilizing an inexpensive amino amide as a transient directing group. In the presence of an electrophilic fluorinating bystanding oxidant and fluorinated alcohols, a wide range of benzaldehydes and benzylic amines could be oxygenated selectively at the ortho positions to afford fluoroalkyl aryl ethers. This elegant approach would provide appealing strategies for synthesis of drug molecules and natural products.

EGFR and ERK activation resists flavonoid quercetin-induced anticancer activities in human cervical cancer cells in vitro.

In the present study, due to the complex and numerous targets of Sarcandrae Herb (also known as Zhong Jie Feng), network pharmacology was performed to analyze its therapeutic effect on 2 cervical cancer cell lines, which could assist with the development of novel therapies. The results suggested that the natural flavonoid quercetin (Que), the effective antitumor ingredient in SH, which is widely present in a variety of plants, may depend on the target, EGFR. Previous studies have shown that EGFR serves a crucial role in the occurrence and development of cervical cancer, but its downstream molecules and regulatory mechanisms remain unknown. The anti-cervical cancer cell properties of Que, which are present in ubiquitous plants, were examined in vitro to identify the association between Que and its underlying pathway using MTT assays, flow cytometry, western blot analysis and Transwell assays. It was found that Que reduced cervical cancer cell viability, promoted G2/M phase cell cycle arrest and cell apoptosis, as well as inhibited cell migration and invasion. The Tyr1068 phosphorylation site of EGFR and the corresponding ERK target were also examined and the 2 kinases were markedly activated by Que. Furthermore, the EGFR inhibitor, afatinib and the ERK inhibitor, U0126 blocked the increase of EGFR and ERK phosphorylation, and resulted in a notable enhancement of apoptosis and cell cycle arrest. Therefore, to the best of our knowledge, the current results provided the first evidence that EGFR and ERK activation induced by Que could resist Que-induced anticancer activities. On this basis, the present study determined the role of EGFR and the underlying signaling pathways involved in the anti-cervical cancer malignant behavior induced by Que and identified the negative regulatory association.

Association between the rs3733846 in the flanking region of miR-143/145 and risk of cervical squamous cell carcinoma.

Aim: To investigate the effect of rs3733846 in the flanking region of miR-143/145 on susceptibility to cervical squamous cell carcinoma (CSCC). Materials & methods: We collected venous blood samples from 242 CSCC patients and 250 healthy controls. The rs3733846 polymorphism was genotyped by SnaPshot and Sanger sequencing. The expression of miR-143/145 in CSCC tissues was detected by quantitative real-time PCR. Results: The rs3733846 AG genotype was associated with a decreased risk of CSCC in genetic model (AGvs.AA: adjusted odds ratio [OR]: 0.44; 95% CI: 0.30-0.66; p < 0.001). Patients with the rs3733846 AG/GG genotypes had a reduced risk of developing poorly differential status (OR: 0.57; 95% CI: 0.33-0.98; p < 0.04) and lymph node metastasis (OR: 0.49; 95% CI: 0.26-0.92; p < 0.03). Conclusion: The rs3733846 in the flanking region of miR-143/145 was related to the susceptibility of CSCC.

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment.

PURPOSE: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment. METHODS: By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation. RESULTS: With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9±1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96±1.88)% compared with (0.99±0.10)% in PBS group, revealing the enhanced immune response against PCa. CONCLUSION: The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy.

ERK Activation-Mediated Autophagy Induction Resists Licochalcone A-Induced Anticancer Activities in Lung Cancer Cells in vitro.

INTRODUCTION: The incidence and mortality rates of lung cancer rank top in the different types of cancers in China. Licochalcone A (LA) is a flavonoid extracted from the roots of licorice with antitumor effects in various cancers in vitro and in vivo. However, the role of LA in non-small cell lung cancer (NSCLC) remains largely unclear. METHODS: The cell viability was measured by MTT assay, Edu staining and colony formation assay. Apoptosis was investigated using Annexin V/PI double-stained assays with flow cytometry. Real-time quantitative RT-PCR was carried out to investigate the expression of mRNA of related proteins. Western blotting was used to investigate the expression of related proteins. RESULTS: The results show that LA inhibits the proliferation of NSCLC cells in a dose-dependent manner and induces apoptotic cell death. Moreover, LA significantly suppresses the expression of c-IAP1, c-IAP2, XIAP, Survivin, c-FLIPL and RIP1 without influencing the level of mRNA. Cycloheximide chase assay demonstrates that LA greatly decreases the stability of Survivin, XIAP and RIP1. Mechanistic studies indicate that LA induces cytoprotective autophagy since block of autophagy with CQ greatly enhances LA-induced anticancer activities. Furthermore, LA rapidly induces ERK and p38 activation in a time-dependent manner in both A549 and H460 cells, but suppresses the activities of c-Jun N-terminal kinase (JNK); suppression of ERK not p38 with inhibitor attenuates LA-induced autophagy, while it remarkably enhances LA-induced cytotoxicity in lung cancer cells and further promotes the degradation of apoptosis-related proteins. DISCUSSION: The results of this study provide novel insights on the role of apoptosis-related proteins and the MAPKs pathway in the anticancer activities of LA.