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Targeted Nanoparticle‐Mediated Gene Therapy Mimics Oncolytic Virus for Effective Melanoma Treatment 下载免费PDF全文
Li Luo Yuping Yang Ting Du Tianyi Kang Meimei Xiong Hao Cheng Yu Liu Yujiao Wu Yang Li Yuwen Chen Qianqian Zhang Xuan Liu Xiawei Wei Peng Mi Zhigang She Guangping Gao Yuquan Wei Maling Gou 《Advanced functional materials》2018,28(29)
Oncolytic virus has potential applications in cancer therapy. However, its clinical application is restricted by the virus‐associated biosafety issues. Here, inspired by the key role of vesicular stomatitis virus matrix protein (VSVMP) in the oncolytic vesicular stomatitis virus (VSV) induced apoptosis, a targeted nanoparticle‐delivered neutral VSVMP gene formulation is designed to act like the VSV for cancer therapy. This VSVMP formulation consists of a CRGDKGPDC peptide modified hybrid monomethoxy poly (ethylene glycol)‐poly(d ,l ‐lactide) nanoparticles complexed with VSVMP plasmid, having good blood compatibility and tumor targeting ability. The transfection efficiency is as high as that of VSV. After intravenous administration, the VSVMP formulation can efficiently target the tumor, significantly inhibit the melanoma growth and metastasis, prolong the survival time of tumor‐bearing mice, and does not cause obvious systemic toxicity. The anticancer mechanisms involve apoptosis induction, angiogenesis inhibition and some virus‐associated signal pathways activation. This work demonstrates a VSV‐inspired nonviral gene therapy that has promising clinical applications in melanoma treatment. 相似文献
53.
多光谱成像(MSI)融合了光谱技术与成像技术,可并行获取探测目标的光谱特征和空间信息。由于采用非侵入式的成像方式,该技术在生物医学领域有很多重要的应用。介绍了多光谱成像的基本原理与技术发展,并从病理研究、手术引导、生物识别等三个方面对其应用进行简要综述。 相似文献
54.
微阵列基因数据用以挖掘特定的生物信息,聚类分析对于研究基因功能和基因调控机制有重要意义.结合改进的遗传算法对基因微阵列数据进行聚类分析,并且通过实验与K均值聚类进行比较.仿真实验表明,该算法可以有效改进基因微阵列数据的聚类准确率. 相似文献
55.
Cancer is a genetic disease originating from the accumulation of gene mutations in a cellular subpopulation. Although many therapeutic approaches have been developed to treat cancer, recent studies have revealed an irrefutable challenge that tumors evolve defenses against some therapies. Gene therapy may prove to be the ultimate panacea for cancer by correcting the fundamental genetic errors in tumors. The engineering of nanoscale inorganic carriers of cancer therapeutics has shown promising results in the efficacious and safe delivery of nucleic acids to treat oncological diseases in small-animal models. When these nanocarriers are used for co-delivery of gene therapeutics along with auxiliary treatments, the synergistic combination of therapies often leads to an amplified health benefit. In this review, an overview of the inorganic nanomaterials developed for combinatorial therapies of gene and other treatment modalities is presented. First, the main principles of using nucleic acids as therapeutics, inorganic nanocarriers for medical applications and delivery of gene/drug payloads are introduced. Next, the utility of recently developed inorganic nanomaterials in different combinations of gene therapy with each of chemo, immune, hyperthermal, and radio therapy is examined. Finally, current challenges in the clinical translation of inorganic nanomaterial-mediated therapies are presented and outlooks for the field are provided. 相似文献
56.
目的:探讨超声微泡介导基因转染面神经的可行性及有效性。方法:建立小鼠面神经损伤模型,以增强型绿色荧光蛋白质粒(pEGFP)为标记基因。将48只小鼠随机分为6组:空白组(A组)、脂质体+质粒组(B组)、微泡+质粒+超声组(C组)、微泡+质粒组(D组)、超声+质粒组(E组)、单纯质粒组(F组)。将小鼠面神经损伤后,局部注射... 相似文献
57.
Nitsa Buaron Antonella Mangraviti Francesco Volpin Ann Liu Mariangela Pedone Eric Sankey Dina Aranovich Itay Adar Fausto J. Rodriguez Abraham Nyska Riki Goldbart Tamar Traitel Henry Brem Betty Tyler Joseph Kost 《Advanced functional materials》2021,31(44):2100643
Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases. 相似文献
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59.
目的:探讨移植转染pDsVEGF165Redl-N1质粒的神经干细胞对脑外伤大鼠的神经保护作用及机制。方法:由新生大鼠脑组织分离培养神经干细胞,应用Lipofectamine2000介导pDsVEGF16sRed1-N1质粒转染神经干细胞;分别将PBS(A组)、神经干细胞(B组)、转基因神经干细胞(C组)移植到脑外伤大鼠局部损伤灶边缘;利用ELISA法检测转基因细胞在体内的表达情况,以免疫组化检测移植后局部损伤组织中微血管密度变化,通过NSS评分评价移植后大鼠神经功能的变化。结果:转基因细胞移植后在一定时间内持续表达VEGFl65,C组大鼠NSS评分从移植后第3天开始明显低于A组(P〈0.05),而B组大鼠NSS评分则从移植后第7天开始明显低于A组(P〈0.05),C组大鼠微血管密度从移植后第7天开始明显高于其他两组(P〈0.01)。结论:转基因神经干细胞表达的VEGF165既可以通过促进微血管再生和改善微循环发挥保护作用又可以直接作用于神经细胞发挥保护作用。 相似文献
60.
Wei Yuan Chunyan Li Chen Zhao Chenguang Sui Wan‐Tai Yang Fu‐Jian Xu Jie Ma 《Advanced functional materials》2012,22(9):1835-1842
Efficient local gene transfection on a tissue scaffold is of crucial importance in facilitating tissue repair and regeneration. In this work, the gelatin‐functionalized polycaprolactone (PCL) film surfaces are prepared via surface‐initiated atom transfer radical polymerization of glycidyl methacrylate. The resultant covalent attachment of gelatin could enhance the cell‐adhesion and local gene transfection properties. The gelatin‐functionalized PCL film surfaces exhibit excellent cell‐adhesion ability to both adherent and suspension cells. The attached adherent cells demonstrate the characteristic elongated morphologies with good spreading capability, while the attached suspension cells can maintain the original status of the round morphologies without spreading. More importantly, the gelatin coupled on the PCL surface could be used to absorb the cationic vector/plasmid deoxyribonucleic acid (pDNA) complexes via electrostatic interaction. The local gene transfection property on the immobilized cells is dependent on both the density of the immobilized cells and the loading types of pDNA complexes. The transfection efficiency of different assemble methods of pDNA complex was compared. With the pre‐ and post‐loading sandwich‐like gene transfection, the gelatin‐functionalized PCL film surface can substantially enhance the transfection properties to different cell lines. The present study is very useful to spatially control local gene delivery within PCL‐based tissue scaffolds. 相似文献