This work aimed to develop an intelligent multi-target tracking hyaluronic acid-RGDchlorambucil-quantum dots（HA-RGD-CLB-QDs） drug delivery system. After deacetylated, hyaluronic acid was reacted with anticancer drug...This work aimed to develop an intelligent multi-target tracking hyaluronic acid-RGDchlorambucil-quantum dots（HA-RGD-CLB-QDs） drug delivery system. After deacetylated, hyaluronic acid was reacted with anticancer drug chlorambucil, RGD, and quantum dots to obtain the HA-RGD-CLB-QDs drug delivery system. The characterization by FT-IR, ~1 H NMR, TEM, XPS, DLS, and UV-vis absorption and fluorescence spectra show that the system is successfully constructed with an average particle size of about 70 nm. The results of the drug release profile show that that the system has a p H and enzyme sensitive controlled release behaviour. Moreover, cellular uptake and toxicity results show that the system has an ideal dual receptormediated endocytosis pathway that significantly enhances the efficacy of CLB tumor therapy and has a lower toxicity to normal cells.The system shows the potential application as a carrier for cancer therapy.展开更多
A dual-receptor targeting delivery system based on acid-cleavage hydrazone bond was developed in the study. The characters of CMCS-hyd-CUR-EGFR-mAb were identified. The in vitro release studies revealed that this drug...A dual-receptor targeting delivery system based on acid-cleavage hydrazone bond was developed in the study. The characters of CMCS-hyd-CUR-EGFR-mAb were identified. The in vitro release studies revealed that this drug delivery system was acid-sensitive, and the self-assembled nanoparticles which were spherical. The in vitro results indicated that the dual-receptor targeting nanoparticles could be faster internalized into the Cal-27 cells via receptor-mediated endocytosis, which exhibited better antitumor activity than the one-receptor nanoparticles. The experimental results clearly reveal that CMCS-hyd-CUR-EGFR mAb provides a novel way for drug delivery in oral cancer treatment.展开更多
<strong>Aim: </strong>In this review paper we propose a method to make an early diagnosis of the Alzheimer’s Disease (AD), the most common form of neurodegenerative dementia. <strong>Background:<...<strong>Aim: </strong>In this review paper we propose a method to make an early diagnosis of the Alzheimer’s Disease (AD), the most common form of neurodegenerative dementia. <strong>Background:</strong> Glymphatic System (GS) is the main means of eliminating waste substances in the central nervous system (CNS);if it does not work properly, waste substances accumulate in CNS until to cause AD. Basal Forebrain is the most important component of a much broader system of cholinergic cells distributed throughout the Central Nervous System (CNS). This structure regulates attention, learning and memory and its destruction is considered responsible for the cognitive AD alterations. The characteristics of AD patients, that interest us most, are the lack of Acetylcholine, and the Orexin excess;we think that the hypothalamus produces more Orexin to stimulate cholinergic cells, indispensable for a correct CNS functioning. We want to identify these patients by detecting the Orexin excess. Early Diagnosis Model. Of course we could take a cerebrospinal fluid sample and dose Orexin but this method is risky and painful for the patient’s health, therefore unsuitable for large numbers of patients. We propose a fairly simple method for the early diagnosis of AD: if we temporarily eliminate the Orexin excess, with Dual Orexin Receptor Antagonist (DORA), i.e. Suvorexant, we can intercept the Orexin increase and demonstrate the decrease in Acetylcholine with a Functional Magnetic Resonance or a Polysomnography, many years before the AD symptoms occur.展开更多
本研究旨在建立一种基于双荧光素酶报告基因检测体系的法尼醇X受体(farnesoid X receptor,FXR)激动剂细胞筛选体系,以满足对FXR激动剂先导化合物的高通量筛选。通过在报告基因质粒pGL4-luc2P-Hygro中的萤火虫荧光素酶(firefly luciferas...本研究旨在建立一种基于双荧光素酶报告基因检测体系的法尼醇X受体(farnesoid X receptor,FXR)激动剂细胞筛选体系,以满足对FXR激动剂先导化合物的高通量筛选。通过在报告基因质粒pGL4-luc2P-Hygro中的萤火虫荧光素酶(firefly luciferase,Luc)基因上游克隆并插入来自FXR靶基因的FXR反应元件(FXR response element,FXRE)片段,构建用于筛选FXR激动剂的报告基因质粒,并结合海肾荧光素酶内参质粒,建立能够有效反映药物对FXR激动效应的双荧光素酶报告基因细胞检测体系。通过一系列优化实验,比较了过表达RXR、鼠源和人源FXR、不同的FXRE片段、FXR过表达质粒与报告基因质粒的混合比对筛选体系诱导效率和灵敏度的影响。根据上述结果,最终确定了优化条件,优化后体系Z因子达到0.83。本研究建立了一种用于FXR激动剂筛选的改良的基于双荧光素酶报告基因检测体系的细胞筛选体系,其主要特征在于,使用多段FXR靶基因上的FXRE片段叠加组成一种新型的增强型FXRE元件,而非传统的反向重复序列-1(inverted repeats-1,IR-1)片段的叠加,为FXR激动剂的发现提供了更好的手段和工具。展开更多
基金Funded by the National Natural Science Foundation of China(Nos.51473130 and 51572206)the Wuhan Huanghe Excellence Plan and Entrepreneurship Training Program of Wuhan University and Technology(Nos.20171049720018,20171049720019 and 20171049720009)
文摘This work aimed to develop an intelligent multi-target tracking hyaluronic acid-RGDchlorambucil-quantum dots（HA-RGD-CLB-QDs） drug delivery system. After deacetylated, hyaluronic acid was reacted with anticancer drug chlorambucil, RGD, and quantum dots to obtain the HA-RGD-CLB-QDs drug delivery system. The characterization by FT-IR, ~1 H NMR, TEM, XPS, DLS, and UV-vis absorption and fluorescence spectra show that the system is successfully constructed with an average particle size of about 70 nm. The results of the drug release profile show that that the system has a p H and enzyme sensitive controlled release behaviour. Moreover, cellular uptake and toxicity results show that the system has an ideal dual receptormediated endocytosis pathway that significantly enhances the efficacy of CLB tumor therapy and has a lower toxicity to normal cells.The system shows the potential application as a carrier for cancer therapy.
基金Funded by the National Natural Science Foundation of China(Nos.81771080 and 8131147)the Opening Project of Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients(No.HLPAI 2014006)the Health Commission of Hubei Province Scientific Research Project(No.WJ2019H275)
文摘A dual-receptor targeting delivery system based on acid-cleavage hydrazone bond was developed in the study. The characters of CMCS-hyd-CUR-EGFR-mAb were identified. The in vitro release studies revealed that this drug delivery system was acid-sensitive, and the self-assembled nanoparticles which were spherical. The in vitro results indicated that the dual-receptor targeting nanoparticles could be faster internalized into the Cal-27 cells via receptor-mediated endocytosis, which exhibited better antitumor activity than the one-receptor nanoparticles. The experimental results clearly reveal that CMCS-hyd-CUR-EGFR mAb provides a novel way for drug delivery in oral cancer treatment.
文摘<strong>Aim: </strong>In this review paper we propose a method to make an early diagnosis of the Alzheimer’s Disease (AD), the most common form of neurodegenerative dementia. <strong>Background:</strong> Glymphatic System (GS) is the main means of eliminating waste substances in the central nervous system (CNS);if it does not work properly, waste substances accumulate in CNS until to cause AD. Basal Forebrain is the most important component of a much broader system of cholinergic cells distributed throughout the Central Nervous System (CNS). This structure regulates attention, learning and memory and its destruction is considered responsible for the cognitive AD alterations. The characteristics of AD patients, that interest us most, are the lack of Acetylcholine, and the Orexin excess;we think that the hypothalamus produces more Orexin to stimulate cholinergic cells, indispensable for a correct CNS functioning. We want to identify these patients by detecting the Orexin excess. Early Diagnosis Model. Of course we could take a cerebrospinal fluid sample and dose Orexin but this method is risky and painful for the patient’s health, therefore unsuitable for large numbers of patients. We propose a fairly simple method for the early diagnosis of AD: if we temporarily eliminate the Orexin excess, with Dual Orexin Receptor Antagonist (DORA), i.e. Suvorexant, we can intercept the Orexin increase and demonstrate the decrease in Acetylcholine with a Functional Magnetic Resonance or a Polysomnography, many years before the AD symptoms occur.
