Xiaotian Zhao

Potential Value of miR-221/222 as Diagnostic, Prognostic, and Therapeutic Biomarkers for Diseases

microRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by base pairing with their target messenger RNAs. Dysregulation of miRNAs is involved in the pathological initiation and progression of many human diseases. miR-221 and miR-222 (miR-221/222) are two highly homologous miRNAs, and they are significantly overexpressed in several types of human diseases. Silencing miR-221/222 could represent a promising approach for therapeutic studies. In the present review, we will describe the potential value of miR-221/222 as diagnostic, prognostic, and therapeutic biomarkers in various diseases including cancer and inflammatory diseases.

Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush

MicroRNA (miRNA) has great potential to treat a wide range of illnesses by regulating the expression of eukaryotic genes. Biomaterials with high transfection efficiency and low toxicity are needed to deliver miRNA to target cells. In this study, a biodegradable and biocompatible cationic polymer (PDAPEI) was synthetized from low molecular weight polyethyleneimine (PEI1.8kDa) cross-linked with 2,6-pyridinedicarboxaldehyde. PDAPEI showed a lower cytotoxicity and higher transfection efficiency than PEI25kDa in transfecting miR-221/222 into rat Schwann cells (SCs). The upregulation of miR-221/222 in SCs promoted the expression of nerve growth factor and myelin basic protein in vitro. The mouse sciatic nerve crush injury model was used to evaluate the effectiveness of PDAPEI/miR-221/222 complexes for nerve regeneration in vivo. The results of electrophysiological tests, functional assessments, and histological and immunohistochemistry analyses demonstrated that PDAPEI/miR-221/222 complexes significantly promoted nerve regeneration after sciatic nerve crush, specifically enhancing remyelination. All these results show that the use of PDAPEI to deliver miR-221/222 may provide a safe therapeutic means of treating nerve crush injury and may help to overcome the barrier of biomaterial toxicity and low efficiency often encountered during medical intervention.

An integrated multi-layer 3D-fabrication of PDA/RGD coated graphene loaded PCL nanoscaffold for peripheral nerve restoration

As a conductive nanomaterial, graphene has huge potentials in nerve function restoration by promoting electrical signal transduction and metabolic activities with unique topological properties. Polydopamine (PDA) and arginylglycylaspartic acid (RGD) can improve cell adhesion in tissue engineering. Here we report an integrated 3D printing and layer-by-layer casting (LBLC) method in multi-layered porous scaffold fabrication. The scaffold is composed of single-layered graphene (SG) or multi-layered graphene (MG) and polycaprolactone (PCL). The electrically conductive 3D graphene scaffold can significantly improve neural expression both in vitro and in vivo. It promotes successful axonal regrowth and remyelination after peripheral nerve injury. These findings implicate that graphene-based nanotechnology have great potentials in peripheral nerve restoration in preclinical and clinical application.Graphene, as a conductive nanomaterial, has potential applications in the restoration of nerve function following physical injury. Here the authors design a graphene scaffold that can improve nerve regeneration.

Immune Activities of Polycationic Vectors for Gene Delivery

Polycationic vectors are used widely in the field of gene delivery, while currently their immune activities in vivo are poorly understood. In this comprehensive review, we aim to present an overview of existing mechanisms of adverse immune responses induced by the polycation/gene complexes, which includes the polycations themselves, the gene sequences and the ROS produced by them. These causes can induce pro-inflammatory cytokines, hypersensitivity as well as the activation of toll-like receptors, and finally the immunostimulation occur. In addition, we introduce some different opinions and research results on the immunogenicity of classical polycations such as polylysine (PLL), polyethyleneimine (PEI), polyamidoamine dendrimers (PAMAM), chitosan and gelatin, most of which have immunogenicity and can induce immunoreactions in vivo. The methods now used to adjust their immunogenicity are shown in the final part of this review. Nowadays, there is still no accurate conclusion on immunogenicity of polycations, which confuses researchers seriously in in vivo test. We conclude that further research is needed in order to skillfully utilize or inhibit the immunogenicity of these polycationic vectors.

Advances in Roles of miR-132 in the Nervous System

miR-132 is an endogenous small RNA and controls post-transcriptional regulation of gene expression via controlled degradation of mRNA or transcription inhibition. In the nervous system, miR-132 is significant for regulating neuronal differentiation, maturation and functioning, and widely participates in axon growth, neural migration, and plasticity. The miR-132 is affected by factors like mRNA expression, functional redundancy, and signaling cascades. It targets multiple downstream molecules to influence physiological and pathological neuronal activities. MiR-132 can influence the pathogenesis of many diseases, especially in the nervous system. The dysregulation of miR-132 results in the occurrence and exacerbation of neural developmental, degenerative diseases, like Alzheimer’s disease, Parkinson’s disease and epilepsy, neural infection and psychiatric disorders including disturbance of consciousness, cognition and memory, depression and schizophrenia. Regulation of miR-132 expression relieves symptoms, alleviates severity and finally effects a cure. This review aims to discuss the clinical potentials of miR-132 in the nervous system.

Asymmetrical Polymer Vesicles for Drug delivery and Other Applications

Scientists have been attracted by polymersomes as versatile drug delivery systems since the last two decades. Polymersomes have the potential to be versatile drug delivery systems because of their tunable membrane formulations, stabilities in vivo, various physicochemical properties, controlled release mechanisms, targeting abilities, and capacities to encapsulate a wide range of drugs and other molecules. Asymmetrical polymersomes are nano- to micro-sized polymeric capsules with asymmetrical membranes, which means, they have different outer and inner coronas so that they can exhibit better endocytosis rate and endosomal escape ability than other polymeric systems with symmetrical membranes. Hence, asymmetrical polymersomes are highly promising as self-assembled nano-delivery systems in the future for in vivo therapeutics delivery and diagnostic imaging applications. In this review, we prepared a summary about recent research progresses of asymmetrical polymersomes in the following aspects: synthesis, preparation, applications in drug delivery and others.

Iron Oxide Nanoparticles-Based Vaccine Delivery for Cancer Treatment

Modern therapeutic cancer vaccines need simple and effective formulations to enhance both humoral and cellular immune responses. Nanoparticles have obtained more and more attention in the development of vaccine delivery platforms. Moreover, nanoparticles-based vaccine delivery platform has high potential for improving the immunogenicity of vaccine. The Food and Drug Administration (FDA) has approved many types of iron oxide nanoparticles for clinical use, such as treating iron deficiency, contrast agents for magnetic resonance imaging (MRI) and drug delivery platforms. In this study, we explored a novel combined use of iron oxide nanoparticles (superparamagnetic Fe3O4 nanoparticles) as a vaccine delivery platform and immune potentiator, and investigated how this formulation affected cytokine expression in macrophages and dendritic cells (DCs) in vitro and tumor growth in vivo. Comparing with soluble OVA alone and iron oxide nanoparticles alone, we found significant differences in immune responses and tumor inhibition induced by OVA formulated with iron oxide nanoparticles. Our iron oxide nanoparticles greatly promoted the activation of immune cells and cytokine production, inducing potent humoral and cellular immune responses. These results suggest that this nanoparticle-based delivery system has strong potential to be utilized as a general platform for cancer vaccines.

3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration

Peripheral nerve defect is a common and severe kind of injury in traumatic accidents. Melatonin can improve peripheral nerve recovery by inhibiting oxidative stress and inflammation after traumatic insults. In addition, it triggers autophagy pathways to increase regenerated nerve proliferation and to reduce apoptosis. In this study, we fabricated a melatonin‐controlled‐release scaffold to cure long‐range nerve defects for the first time. 3D manufacture of melatonin/polycaprolactone nerve guide conduit increased Schwann cell proliferation and neural expression in vitro and promoted functional, electrophysiological and morphological nerve regeneration in vivo. Melatonin nerve guide conduit ameliorated immune milieu by reducing oxidative stress, inflammation and mitochondrial dysfunction. In addition, it activated autophagy to restore ideal microenvironment, to provide energy for nerves and to reduce nerve cell apoptosis, thus facilitating nerve debris clearance and neural proliferation. This innovative scaffold will have huge significance in the nerve engineering.

Advances in redox-responsive drug delivery systems of tumor microenvironment

AbstractWith the improvement of nanotechnology and nanomaterials, redox-responsive delivery systems have been studied extensively in some critical areas, especially in the field of biomedicine. The system constructed by redox-responsive delivery can be much stable when in circulation. In addition, redox-responsive vectors can respond to the high intracellular level of glutathione and release the loaded cargoes rapidly, only if they reach the site of tumor tissue or targeted cells. Moreover, redox-responsive delivery systems are often applied to significantly improve drug concentrations in targeted cells, increase the therapeutic efficiency and reduce side effects or toxicity of primary drugs. In this review, we focused on the structures and types of current redox-responsive delivery systems and provided a comprehensive overview of relevant researches, in which the disulfide bond containing delivery systems are of the utmost discussion.

pH-Responsive Cross-Linked Low Molecular Weight Polyethylenimine as an Efficient Gene Vector for Delivery of Plasmid DNA Encoding Anti-VEGF-shRNA for Tumor Treatment

RNA interference (RNAi) is a biological process through which gene expression can be inhibited by RNA molecules with high selectivity and specificity, providing a promising tool for tumor treatment. Two types of molecules are often applied to inactivate target gene expression: synthetic double stranded small interfering RNA (siRNA) and plasmid DNA encoding short hairpin RNA (shRNA). Vectors with high transfection efficiency and low toxicity are essential for the delivery of siRNA and shRNA. In this study, TDAPEI, the synthetic derivative of low-molecular-weight polyethylenimine (PEI), was cross-linked with imine bonds by the conjugation of branched PEI (1.8 kDa) and 2,5-thiophenedicarboxaldehyde (TDA). This biodegradable cationic polymer was utilized as the vector for the delivery of plasmid DNA expressing anti-VEGF-shRNA. Compared to PEI (25 kDa), TDAPEI had a better performance since experimental results suggest its higher transfection efficiency as well as lower toxicity both in cell and animal studies. TDAPEI did not stimulate innate immune response, which is a significant factor that should be considered in vector design for gene delivery. All the results suggested that TDAPEI delivering anti-VEGF-shRNA may provide a promising method for tumor treatment.