Simultaneous Imaging and Photodynamic-Enhanced Photothermal Inhibition of Cancer Cells Using a Multifunctional System Combining Indocyanine Green and Polydopamine-Preloaded Upconversion Luminescent Nanoparticles.

This work introduces a novel multifunctional system called UPIPF (upconversion-polydopamine-indocyanine-polyethylene-folic) for upconversion luminescent (UCL) imaging of cancer cells using near-infrared (NIR) illumination. The system demonstrates efficient inhibition of human hepatoma (HepG2) cancer cells through a combination of NIR-triggered photodynamic therapy (PDT) and enhanced photothermal therapy (PTT). Initially, upconversion nanoparticles (UCNP) are synthesized using a simple thermal decomposition method. To improve their biocompatibility and aqueous dispersibility, polydopamine (PDA) is introduced to the UCNP via a ligand exchange technique. Indocyanine green (ICG) molecules are electrostatically attached to the surface of the UCNP-polydopamine (UCNP@PDAs) complex to enhance the PDT and PTT effects. Moreover, polyethylene glycol (PEG)-modified folic acid (FA) is incorporated into the UCNP-polydopamine-indocyanine-green (UCNP@PDA-ICGs) nanoparticles to enhance their targeting capability against cancer cells. The excellent UCL properties of these UCNP enable the final UCNP@PDA-ICG-PEG-FA nanoparticles (referred to as UPIPF) to serve as a potential candidate for efficient anticancer drug delivery, real-time imaging, and early diagnosis of cancer cells. Furthermore, the UPIPF system exhibits PDT-assisted PTT effects, providing a convenient approach for efficient cancer cell inhibition (more than 99% of cells are killed). The prepared UPIPF system shows promise for early diagnosis and simultaneous treatment of malignant cancers.

Cytotoxicity and cell death induced by engineered nanostructures (quantum dots and nanoparticles) in human cell lines.

In recent years, the industrial use of ZnO quantum dots (QDs) and nanoparticles (NPs) has risen and there is a high chance of these nanoparticles affecting human health. In this study, different sizes of ZnO-NPs (6-100 nm) were prepared and characterized. The generation of reactive oxygen species (ROS) and its involvement in apoptosis when HepG2 cells were exposed to QDs (6 nm) and NPs of different sizes (15-20, 50, and 100 nm) was also investigated. At a concentration of 25-200 µg/mL, NPs induced dose-dependent cytotoxicity in HepG2 cells. The engineered NPs increased oxidative stress in a dose- and size-dependent manner, as seen by an increase in ROS production, lipid peroxidation, and glutathione reduction. Furthermore, cell-cycle analysis of HepG2 cells treated with different sizes of NPs showed an increase in the apoptotic peak after a 24-h exposure period. Quantitative real-time PCR data showed that the mRNA levels of apoptotic marker genes such as p53, bax, and caspase-3 were upregulated, whereas bcl-2, an anti-apoptotic gene, was downregulated; therefore, apoptosis was mediated through the p53, bax, caspase-3, and bcl-2 pathways, suggesting a possible mechanism by which QDs and NPs of ZnO mediate their toxicity.Graphic abstract.

Staurosporine suppresses survival of HepG2 cancer cells through Omi/HtrA2-mediated inhibition of PI3K/Akt signaling pathway.

Staurosporine, which is an inhibitor of a broad spectrum of protein kinases, has shown cytotoxicity on several human cancer cells. However, the underlying mechanism is not well understood. In this study, we examined whether and how this compound has an inhibitory action on phosphatidylinositol 3-kinase (PI3K)/Akt pathway in vitro using HepG2 human hepatocellular carcinoma cell line. Cell viability and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, respectively. Glutathione S-transferase (GST) pull-down assay and co-immunoprecipitation were performed to detect protein-protein interactions. Small interfering RNA (siRNA) was used to silence the expression of targeted protein. We found that staurosporine significantly decreased cell viability and increased cell apoptosis in a concentration- and time-dependent manner in HepG2 cancer cells, along with the decreased expressions of PDK1 protein and Akt phosphorylation. Staurosporine was also found to enhance Omi/HtrA2 release from mitochondria. Furthermore, Omi/HtrA2 directly bound to PDK1. Pharmacological and genetic inhibition of Omi/HtrA2 restored protein levels of PDK1 and protected HepG2 cancer cells from staurosporine-induced cell death. In addition, staurosporine was found to activate autophagy. However, inhibition of autophagy exacerbated cell death under concomitant treatment with staurosporine. Taken together, our results indicate that staurosporine induced cytotoxicity response by inhibiting PI3K/Akt signaling pathway through Omi/HtrA2-mediated PDK1 degradation, and the process provides a novel mechanism by which staurosporine produces its therapeutic effects.

Pluronic-F-127-Passivated SnO2 Nanoparticles Derived by Using Polygonum cuspidatum Root Extract: Synthesis, Characterization, and Anticancer Properties.

Nanotechnology has emerged as the most popular research topic with revolutionary applications across all scientific disciplines. Tin oxide (SnO2) has been gaining considerable attention lately owing to its intriguing features, which can be enhanced by its synthesis in the nanoscale range. The establishment of a cost-efficient and ecologically friendly procedure for its production is the result of growing concerns about human well-being. The novelty and significance of this study lie in the fact that the synthesized SnO2 nanoparticles have been tailored to have specific properties, such as size and morphology. These properties are crucial for their applications. Moreover, this study provides insights into the synthesis process of SnO2 nanoparticles, which can be useful for developing efficient and cost-effective methods for large-scale production. In the current study, green Pluronic-coated SnO2 nanoparticles (NPs) utilizing the root extracts of Polygonum cuspidatum have been formulated and characterized by several methods such as UV-visible, Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDAX), transmission electron microscope (TEM), field emission-scanning electron microscope (FE-SEM), X-ray diffraction (XRD), photoluminescence (PL), and dynamic light scattering (DLS) studies. The crystallite size of SnO2 NPs was estimated to be 45 nm, and a tetragonal rutile-type crystalline structure was observed. FESEM analysis validated the NPs' spherical structure. The cytotoxic potential of the NPs against HepG2 cells was assessed using the in vitro MTT assay. The apoptotic efficiency of the NPs was evaluated using a dual-staining approach. The NPs revealed substantial cytotoxic effects against HepG2 cells but failed to exhibit cytotoxicity in different liver cell lines. Furthermore, dual staining and flow cytometry studies revealed higher apoptosis in NP-treated HepG2 cells. Nanoparticle treatment also inhibited the cell cycle at G0/G1 stage. It increased oxidative stress and promoted apoptosis by encouraging pro-apoptotic protein expression in HepG2 cells. NP treatment effectively blocked the PI3K/Akt/mTOR axis in HepG2 cells. Thus, green Pluronic-F-127-coated SnO2 NPs exhibits enormous efficiency to be utilized as an talented anticancer agent.

Magnetic implants in vivo guiding sorafenib liver delivery by superparamagnetic solid lipid nanoparticles.

HYPOTHESIS: Solid lipid nanoparticles (SLNs), co-encapsulating superparamagnetic iron oxide nanoparticles and sorafenib, have been exploited for magnetic-guided drug delivery to the liver. Two different magnetic configurations, both comprising two small magnets, were under-skin implanted to investigate the effect of the magnetic field topology on the magnetic SLNP accumulation in liver tissues. A preliminary simulation analysis was performed to predict the magnetic field topography for each tested configuration. EXPERIMENTS: SLNs were prepared using a hot homogenization approach and characterized using complementary techniques. Their in vitro biological behavior was assessed in HepG-2 liver cancer cells; wild-type mice were used for the in vivo study. The magnet configuration that resulted in a higher magnetic targeting efficiency was investigated by evaluating the iron content in homogenated murine liver tissues. FINDINGS: SLNs, characterized by an average size smaller than 200 nm, retained their superparamagnetic behavior and relevant molecular resonance imaging properties as negative contrast agents. The evaluation of iron accumulation in the liver tissues was consistent with the magnetic induction profile of each magnet configuration, concurring with the results predicted by simulation analysis and obtained by measurements in living mice.

Ultrasound-, subcritical water- and ultrasound assisted subcritical water-derived Tartary buckwheat polyphenols show superior antioxidant activity and cytotoxicity in human liver carcinoma cells.

The effects of ultrasound-assisted (UAE), subcritical water (SWE) and ultrasound assisted-subcritical water (UA-SWE) treatments on tartary buckwheat polyphenol yield, composition, antioxidant activity and cytotoxicity in human liver carcinoma cells were studied. Folin Ciocalteu assay was used to measure total free phenol content (TFPC), and ABTS, DPPH, FRAP and TEAC assays were used to measure antioxidant activity (AA). Polyphenol characterization was done by LC-MS and cell antioxidant activity (CAA) and cytotoxicity were done using the 2,2'-Azobis-(2-amidinopropane) dihydrochloride [ABAP] and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide [MTT] assays respectively. The highest polyphenol yield was obtained by SWE (53.3 mg g-1), followed by UA-SWE (31.8 mg g-1), UAE (19.3 mg g-1) and HWE (4.2 mg g-1). Also, SWE had the highest TFPC (7.9 mgGAE/gdw). UAE and UA-SWE showed no differences with TFPC being 6.6 and 6.8 mgGAE/gdw, respectively. The control method (HWE) had the largest number of phenolic compounds identified (25), followed by UAE, SWE and UA-SWE which had 20, 13 and 11 phenolics respectively. Beside phenolic acids, all treatments extracted a number of flavonoids such as flavan-3-ols (catechin-7-O-glucoside, epigallocatechin-3-gallate, epigallocatechin, epicatechin), flavonols (kaempferol-3-O-glucoside, kaempferol, kaempferol-3-rutinoside, rutin, quercetin, quercetin-3-O-glucuronide hyperin), flavones (vitexin, isovitexin, orientin, isoorientin) and anthocyanins (cyanidin-3-O-rutinoside, Cyanidin 3-O-galactoside, cyanidin-3-O-glucoside). SWE gave the highest AA for all tests. However, the AA of those obtained by UAE and UA-SWE did not vary (P < 0.05), but were higher than HWE. Different extracts had best AA at different concentrations (HWE, 300; UAE, 250; SWE, 150; UA-SWE, 200 µg/mL). The IC50 of AA were 270.8 ± 21.3, 198.1 ± 16.0, 97.9 ± 13.5, and 150.4 ± 12.8 µg/mL, respectively for HWE, UAE, SWE and UA-SWE. Generally, SWE and UA-SWE showed the highest cytotoxic activities, followed by UAE, with HWE being the lowest. IC50 of cytotoxicity were 76.1 ± 3.3, 79.5 ± 7.0 and 92.6 ± 4.9 µg/mL for SWE, UA-SWE and UAE, respectively. SWE is a promising method for polyphenol extraction and its combination with ultrasound should be optimized for high yield and conservation of bioactivity.

The Killing Effects and Preliminary Mechanism of Natural Plant-derived Antimicrobial Solution(PAMs)to Human Liver Cancer HEPG-2 Cells / 现代生物医学进展

Objective:In this study,a series of experiments were conducted to research the mechanism of anticancer and preliminary molecular effects of PAMs on the HEPG-2 cancer cells.Methods:Morphological observation and MTT assay were used to explore the inhibition and killing effect of PAMs acting on HEPG-2.AO/EB staining and Annexin V-FITC/PI staining were employed to observe the apoptosis of HEPG-2 treated with PAMs.The expression level of Foxm1,bcl-2 and others genes in HEPG-2 cells were detected by using qRT-PCR and western blot.Wound healing and transwell experiments determined if PAMs can inhibit the migration of HEPG-2.Results:PAMs can inhibit and kill HEPG-2 cells in time and dose-dependent manners,and the cytotoxic effects were closely related to the cell apoptosis.The mRNA expression of foxm1,bcl-2 and surviving gene were remarkably decreased in HEPG-2 cells after the treatment of PAMs.PAMs decreased the FoXM1 protein expression in HEPG-2 cells,while up-regulating thep53 protein expression.,and it could also inhibit the migration of cancer cells.Conclusions:The possible molecular mechanism for the killing of HEPG-2 cancer cells by PAMs was proposed.By down-regulating the expression of foxm1 and up-regulating the expression of p53,the transcriptional expression of their downstream target genes survivin and bcl-2 was inhibited or reduced,hence enhancing the cancer cell apoptosis.This study provides an important foundation for the development of anti-cancer Chinese folk medicine based on PAMs.