Lipoic Acid-Modified Oligoethyleneimine-Mediated miR-34a Delivery to Achieve the Anti-Tumor Efficacy

MiR-34a, an important tumor suppressor, has been demonstrated to possess great potential in tumor gene therapy. To achieve the upregulation of miR-34a expression level, an oligoethyleneimine (OEI) derivative was constructed and employed as the carrier through the modification with lipoic acid (LA), namely LA-OEI. In contrast to OEI, the derivative LA-OEI exhibited superior transfection efficiency measured by confocal laser scanning microscopy and flow cytometry, owing to rapid cargo release in the disulfide bond-based reduction sensitive pattern. The anti-proliferation and anti-migration effects were tested after the miR-34a transfection to evaluate the anti-tumor response, using human cervical carcinoma cell line HeLa as a model. The delivery of LA-OEI/miR-34a nanoparticles could achieve obvious anti-proliferative effect caused by the induction of cell apoptosis and cell cycle arrest at G1 phase. In addition, it could inhibit the migration of tumor cells via the downregulation of MMP-9 and Notch-1 level. Overall, the LA-OEI-mediated miR-34a delivery was potential to be used as an effective way in the tumor gene therapy.

MicroRNA-373-3p inhibits the growth of cervical cancer by targeting AKT1 both in vitro and in vivo

Objective: In this study, we aimed to investigate the function of microRNA-373-3p (miR-373-3p) in the pathogenesis of cervical cancer. Methods: Human and mouse cervical cancer cell lines were transfected with miR-373-3p mimic and inhibitor. Cell proliferation and viability were evaluated with Cell Counting Kit-8 (CCK-8) assay and Lactate Dehydrogenase (LDH) assay, respectively. The AKT1-targeting role of miR-373-3p was analyzed by qPCR and Western blot. Finally, a mouse xenograft cervical tumor model was adopted to study the in vivo effect of miR-373-3p on tumor growth and the expression of AKT1. Results: Over-expression of miR-373-3p significantly reduced the proliferation of cervical carcinoma cell line in vitro. In addition, miR-373-3p overexpression also inhibited cervical cancer growth in tumor-bearing mice. Mechanistically, we found that AKT1 gene can be targeted by miR-373-3p. MiR-373-3p mimic decreased the mRNA and protein expression of AKT1, while the miR-373-3p inhibitor increased the level of AKT1 in cervical cancer cells. AKT1 overexpression rescued the proliferation of cervical cancer cells transfected with miR-373-3p. Conclusion: MiR-373-3p can serve as a novel anti-tumor microRNA in cervical cancer by targeting AKT1.

A Novel BODIPY Quaternary Ammonium Salt-Based Fluorescent Probe: Synthesis, Physical Properties, and Live-Cell Imaging

The development of biological fluorescent probes is of great significance to the field of cancer bio-imaging. However, most current probes within the bulky hydrophobic group have limited application in aqueous medium and restricted imaging under physiological conditions. Herein, we proposed two efficient molecules to study their physical properties and imaging work, and the absorption and fluorescence intensity were collected with varying ions attending in aqueous medium. We enhance the water solubility through the quaternization reaction and form a balance between hydrophilic and hydrophobicity with dipyrrome-theneboron difluoride (BODIPY) fluorophore. We introduced pyridine and dimethylaminopyridine (DMAP) by quaternization and connected the BODIPY fluorophore by ethylenediamine. The final synthesized probes have achieved ideal affinity with HeLa cells (human cervical carcinoma cell line) in live-cell imaging which could be observed by Confocal Microscope. The probes also have a good affinity with subcutaneous tumor cells in mice in in vivo imaging, which may make them candidates as oncology imaging probes.

MODIFICATION OF NANOCRYSTALLINE SILICON BY POLYMERS FOR BIOMEDICAL APPLICATIONS

In this paper, it is proposed to use polymer-modified composite materials based on nanocrystalline silicon (nc-Si) as an alternative to organic fluorescent quantum dots traditionally used in medicine. A distinctive feature of nc-Si is a high absorption coefficient in the near UV and blue-violet range and the ability to transmit light in the visible region of the spectrum. The main advantage of silicon-based nanoparticles for in vivo use is their biodegradability and the absence of toxic properties. For hydrophilization of silicon nanoparticles, their surface was modified by amphiphilic biocompatible polymers: polyvinylpyrrolidone, a copolymer of maleic anhydride and 1-octadecene, cremophore, which is a polyoxyethylene derivative of hydrogenated castor oil. Silicon nanoparticles (nc-Si) with an average diameter of 4.5 nm, synthesized by annealing of SiO at 1150 °C, and functionalized with 1-octadecene photoluminescent in the red-infrared spectral region were used. The presence of the polymer shell on the surface of the nanoparticles was confirmed by FTIR spectroscopy. The sedimentation and aggregative stability of the particles in water were analyzed. It is shown that after the nc-Si polymer modification, the photoluminescent properties of nanoparticles are retained although the photoluminesce maxima were shifted to the blue region. Colorimetric MTT-assay of the cytotoxicity of the nanoparticles modified with polymers to monoclonal cells of human erythroleukemia K562 showed no toxicity for cells in culture at a particle concentration of up to 50 μg/ml. Subcellular localization of silicon nanoparticles into the human cervical carcinoma cell line HeLa was shown by means of fluorescence microscopy. The obtained polymer-modified nc-Si particles can be recommended for the purposes of bioimaging in in vitro and in vivo applications.

The Role of Gold Nanoparticles in Sonosensitization of Human Cervical Carcinoma Cell Line under Ultrasound Irradiation: An In Vitro Study

Purpose: The objective of this investigation was to evaluate the combined effects of ultrasound irradiation as a non-invasive and non-ionizing radiation with gold nanoparticles as ultrasound sensitizers on the HeLa cells.Materials and Methods: First, Gold nanoparticles (GNPs) were prepared, and the characterizations of nanoparticles were analyzed using TEM and UV-vis. Different concentrations of nanoparticles (0.2, 1, 5, 25 and 50 μg/ml) were used. Then, cytotoxicity of the GNPs was studied on HeLa cells, and finally concentrations of 0.2, 1 and 5 µg/mL were chosen for supplementary studies. The effects of nanoparticles and ultrasound irradiation with different intensities (0.5, 1 and 1.5 W/cm2) as well as the combination of ultrasound radiation with various concentrations of nanoparticles on 24, 48 and 72 h post-experiment cells’ viability were estimated by MTT and trypan blue assay.Results: Results showed that the sonosensitizing effect of nanoparticles mainly depended on the intensity of ultrasound waves and the concentration of GNPs. By increasing the concentration of GNPs and ultrasound intensity, the nanoparticle's effect of sensitizer was also increased. Moreover, as expected, the highest effect was observed at the highest intensities (1.5 W/cm2) of ultrasound wave and high concentrations (5 μg/ml) of GNPs 72 h after exposure to ultrasound irradiation.Conclusions: It is revealed that GNPs can be used as sonosensitizers of HeLa cells to ultrasound irradiation in order to produce an efficient treatment.