Neural stem cells (NSCs), capable of ischemia‐homing, regeneration, and differentiation, exert strong therapeutic potentials in treating ischemic stroke, but the curative effect is limited in the ...harsh microenvironment of ischemic regions rich in reactive oxygen species (ROS). Gene transfection to make NSCs overexpress brain‐derived neurotrophic factor (BDNF) can enhance their therapeutic efficacy; however, viral vectors must be used because current nonviral vectors are unable to efficiently transfect NSCs. The first polymeric vector, ROS‐responsive charge‐reversal poly(2‐acryloyl)ethyl(p‐boronic acid benzyl)diethylammonium bromide (B‐PDEA), is shown here, that mediates efficient gene transfection of NSCs and greatly enhances their therapeutics in ischemic stroke treatment. The cationic B‐PDEA/DNA polyplexes can effectively transfect NSCs; in the cytosol, the B‐PDEA is oxidized by intracellular ROS into negatively charged polyacrylic acid, quickly releasing the BDNF plasmids for efficient transcription and secreting a high level of BDNF. After i.v. injection in ischemic stroke mice, the transfected NSCs (BDNF‐NSCs) can home to ischemic regions as efficiently as the pristine NSCs but more efficiently produce BDNF, leading to significantly augmented BDNF levels, which in turn enhances the mouse survival rate to 60%, from 0% (nontreated mice) or ≈20% (NSC‐treated mice), and enables more rapid and superior functional reconstruction.
The first nonviral gene carrier, reactive‐oxygen‐species‐responsive charge‐reversal poly(2‐acryloyl)‐ethyl(p‐boronic acid benzyl)diethylammonium bromide (B‐PDEA), is shown to mediate efficient gene transfection to neural stem cells (NSCs). When BDNF gene plasmids are used, the transfected NSCs homing to the ischemic regions increase animal survival and reconstruct functions.
Abstract α-Mangostin (α-M) is a polyphenolic xanthone that protects and improves the survival of cerebral cortical neurons against Aβ oligomer-induced toxicity in rats. α-M is a potential candidate ...as a treatment for Alzheimer's disease (AD). However, the efficacy was limited by the poor penetration of the drug through the blood–brain barrier (BBB). In this study, we modified the α-M liposome with transferrin (Tf) and investigated the intracellular distribution of liposomes in bEnd3 cells. In addition, the transport of α-M across the BBB in the Tf(α-M) liposome group was examined. In vitro studies demonstrated that the Tf(α-M) liposome could cross the BBB in the form of an integrated liposome. Results of the in vivo studies on the α-M distribution in the brain demonstrated that the Tf(α-M) liposome improved the brain delivery of α-M. These results indicated that the Tf liposome is a potential carrier of α-M against AD.
The heterogeneity of hepatocellular carcinoma (HCC) commonly leads to therapeutic failure of HCC. Cytokeratin 19 (CK19) is well acknowledged as a biliary/progenitor cell marker and a marker of tumor ...stem cell. CK19-positive HCCs demonstrate aggressive behaviors and poor outcomes which including worse overall survival and early tumor recurrence after hepatectomy and liver transplantation. CK19-positive HCCs are resistant to chemotherapies as well as local treatment. This subset of HCC is thought to derive from liver progenitor cells and can be induced by extracellular stimulation such as hypoxia. Besides being a stemness marker, CK19 plays an important role in promoting malignant property of HCC. The regulatory network associated with CK19 expression has been summarized that extracellular stimulations which transmit into cytoplasm through signal transduction pathways (TGF-β, MAKP/JNK and MEK-ERK1/2), further induce important nuclear transcriptional factors (SALL4, AP1, SP1) to activate CK19 promoter. Novel noncoding RNAs are also involved in the regulation of CK19 expression. TGFβR1 becomes a therapeutic target for CK19-positive HCC. In conclusion, CK19 can be a potential biomarker for predicting poor prognosis after surgical and adjuvant therapies. CK19-pisitive HCCs exhibit distinctive molecular profiling, should be diagnosed and treated as a separate subtype of HCCs.
The success of conventional suicide gene therapy for cancer treatment is still limited because of lack of efficient delivery methods, as well as poor penetration into tumor tissues. Mesenchymal stem ...cells (MSCs) have recently emerged as potential vehicles in improving delivery issues. However, these stem cells are usually genetically modified using viral gene vectors for suicide gene overexpression to induce sufficient therapeutic efficacy. This approach may result in safety risks for clinical translation. Therefore, we designed a novel strategy that uses non-viral gene vector in modifying MSCs with suicide genes to reduce risks. In addition, these cells were co-administrated with prodrug-encapsulated liposomes for synergistic anti-tumor effects. Results demonstrate that this strategy is effective for gene and prodrug delivery, which co-target tumor tissues, to achieve a significant decrease in tumor colonization and a subsequent increase in survival in a murine melanoma lung metastasis model. Moreover, for the first time, we demonstrated the permeability of MSCs within tumor nests by using an in vitro 3D tumor spheroid model. Thus, the present study provides a new strategy to improve the delivery problem in conventional suicide gene therapy and enhance the therapeutic efficacy. Furthermore, this study also presents new findings to improve our understanding of MSCs in tumor-targeted gene delivery.
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Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease, thus having attracted much ...attention in recent years. However, their applications are greatly hindered by a lack of safe and efficient oligonucleotide-delivery vectors. Polyplex nanovesicles formed from oligonucleotides and the cationic block have shown exceptional features for the delivery of therapeutic oligonucleotides and other biopharmaceuticals. Nevertheless, these polyplex nanovesicles are deeply fraught with difficulty in tolerating physiological ionic strength. Inspired by the high binding ability between the dipicolylamine (DPA)/zinc (II) complex and the phosphodiester moieties of oligonucleotides, herein, we designed a coordinative cationic block to solve the intrinsic stability dilemma. Moreover, we found the stability of the resulted polyplex nanovesicles could be easily tuned by the content of coordinated zinc ions.
In vitro
cellular studies implied that the prepared zinc (II)-coordinative polyplex nanovesicles preferred to retain in the lysosomes upon internalization, making them ideal delivery candidates for the lysosome-targeting oligonucleotide therapeutics.
Mesoporous silica microspheres, a multifunctional material with high specific surface area, pore size, and mechanical properties, are widely used as separation and support materials. Mesoporous ...silica, has been relatively studied as LC column packing material for separation and detection. In this research, we prepared mesoporous silica microspheres by a simple synthesis method, and the antibacterial modification of mesoporous silica was carried out by adding synthesized PTHP. Excellent test results have been exhibited, the PTHP-SiO
2
mesoporous has the same structure and morphology as the SiO
2
microspheres, but shows excellent bacterial inactivation ability, and better separation as LC column packing material, thus can be applied as a multifunctional material.
Through the study of the molecular formula of p1-AQM2AF, it is found that 9-methylenedecane, as the electron donor system, has strong electron donor capacity, but due to its huge steric hindrance, ...the p1-AQM2AF molecule may be seriously distorted, resulting in the reduction of the fluorescence quantum efficiency of p1-AQM2AF due to the angular momentum energy loss during the electron transmission process. Therefore, we have made a bold guess, The length of alkyl chain may also be one of the factors affecting the fluorescence efficiency of D-A-D conjugated small molecules. We converted the 9-methylene-19decane originally attached to the molecule into 3-methylenenonane, and explored its influence on the fluorescence molecule by reducing the length of the donor alkyl chain.
Column laminating silica gel board plays a very important role in the separation and analysis of organic synthesis, which can monitor the progress of chemical reactions in real time and help ...researchers determine the time when chemical reactions are completed. In this work, we made a modified silicone powder for the separation and analysis of thiophene substances, and found that the modified silicone powder has a better separation effect than commercial silicone powder, which is expected to play a better role in the field of column chromatography separation.
Polymer microspheres have been widely used as a stationary phase in liquid chromatography. We characterized the properties of the novel polyionic liquid microspheres prepared and explored their ...application as a stationary phase in liquid chromatography. Cytosine, uracil, benzene, benzene homologs and alkaloids were successfully separated by liquid chromatography with the polymer microspheres as packing materials in the chromatographic column.
Bacterial infection is a major challenge for contemporary medicine, and antimicrobial hydrogels have been extensively studied for their excellent antimicrobial activity. However, the antibacterial ...agent also has high cytotoxicity and hemolytic activity while being significantly antibacterial. In this paper, we prepared a hydrogel by simple heating-cooling of ZIF-90 doped agar solution, which has obvious antibacterial activity against Gram-positive and Gram-negative bacteria. The test results show that the hydrogel has a uniform and stable structure and does not exhibit cytotoxicity and hemolytic activity while maintaining good bacteriostatic properties, so as to achieve the function of bacterial infection treatment and would healthcare.
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