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The Mg doping ZIF-8 loaded with Icariin and its antibacterial and osteogenic performances 镁掺杂的载Icariin的ZIF-8及其抗菌和成骨性能。
IF 4.2 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2023-10-12 DOI: 10.1007/s10856-023-06755-x
Lili Li, Jianghui Zhao, Fengcang Ma, Daihua He, Ping Liu, Wei Li, Ke Zhang, Xiaohong Chen, Lin Song

In this study, ICA@Mg-ZIF-8 was synthesized by Mg doping in ZIF-8 and loaded with icariin (ICA). The morphologies and phases were observed and analyzed by SEM, XRD, and the release behaviors of Mg, Zn ions and ICA were tested. Its antibacterial and mineralization performances were evaluated. The results showed that ICA@Mg-ZIF-8 has the same morphology and crystal structure as ZIF-8. ICA@Mg-ZIF-8 showed enhanced antibacterial activity against Escherichia coli and Staphylococcus aureus, and the antibacterial rate was increased to 87.7 % and 64.0 %, respectively. The results of in vitro mineralization showed that ICA@Mg-ZIF-8 presented better osteogenic performance promoting the uniform deposition of more calcium and phosphorus in simulated body fluids compared to ZIF-8.

Graphical Abstract

在本研究中,ICA@Mg-ZIF-8通过在ZIF-8中掺杂镁来合成,并负载了icariin(ICA)。通过SEM、XRD对其形貌和相进行了观察和分析,并测试了Mg、Zn离子和ICA的释放行为。对其抗菌和矿化性能进行了评价。结果表明:ICA@Mg-ZIF-8具有与ZIF-8相同的形态和晶体结构。ICA@Mg-ZIF-8对大肠杆菌和金黄色葡萄球菌的抗菌活性增强,抗菌率分别提高到87.7%和64.0%。体外矿化结果表明:ICA@Mg-ZIF-8与ZIF-8相比,ZIF-8具有更好的成骨性能,促进了模拟体液中更多钙和磷的均匀沉积。
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引用次数: 0
Polycaprolactone/graphene oxide/acellular matrix nanofibrous scaffolds with antioxidant and promyelinating features for the treatment of peripheral demyelinating diseases 聚己内酯/氧化石墨烯/无细胞基质纳米纤维支架具有抗氧化和脱髓鞘功能,用于治疗外周脱髓鞘疾病。
IF 4.2 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2023-10-05 DOI: 10.1007/s10856-023-06750-2
Aishwarya Nagarajan, Nasera Rizwana, Michelle Abraham, Mahima Bhat, Aakanksha Vetekar, Goutam Thakur, Uttara Chakraborty, Vipul Agarwal, Manasa Nune

Peripheral demyelinating diseases entail damage to axons and Schwann cells in the peripheral nervous system. Because of poor prognosis and lack of a cure, this group of diseases has a global impact. The primary underlying cause of these diseases involves the inability of Schwann cells to remyelinate the damaged insulating myelin around axons, resulting in neuronal death over time. In the past decade, extensive research has been directed in the direction of Schwann cells focusing on their physiological and neuroprotective effects on the neurons in the peripheral nervous system. One cause of dysregulation in the remyelinating function of Schwann cells has been associated with oxidative stress. Tissue-engineered biodegradable scaffolds that can stimulate remyelination response in Schwann cells have been proposed as a potential treatment strategy for peripheral demyelinating diseases. However, strategies developed to date primarily focussed on either remyelination or oxidative stress in isolation. Here, we have developed a multifunctional nanofibrous scaffold with material and biochemical cues to tackle both remyelination and oxidative stress in one matrix. We developed a nanofibrous scaffold using polycaprolactone (PCL) as a foundation loaded with antioxidant graphene oxide (GO) and coated this bioscaffold with Schwann cell acellular matrix. In vitro studies revealed both antioxidant and remyelination properties of the developed bioscaffold. Based on the results, the developed multifunctional bioscaffold approach can be a promising biomaterial approach for treating demyelinating diseases.

Graphical Abstract

外周脱髓鞘疾病导致外周神经系统中的轴突和雪旺细胞受损。由于预后不良且缺乏治愈方法,这类疾病具有全球影响。这些疾病的主要潜在原因是施旺细胞无法使轴突周围受损的绝缘髓鞘重新髓鞘化,随着时间的推移导致神经元死亡。在过去的十年里,人们对施旺细胞进行了广泛的研究,重点是它们对周围神经系统神经元的生理和神经保护作用。雪旺细胞髓鞘再形成功能失调的一个原因与氧化应激有关。组织工程可生物降解支架可以刺激施旺细胞的髓鞘再生反应,已被认为是外周脱髓鞘疾病的潜在治疗策略。然而,迄今为止制定的策略主要集中在髓鞘再生或单独的氧化应激上。在这里,我们开发了一种具有材料和生物化学线索的多功能纳米纤维支架,以在一个基质中解决髓鞘再生和氧化应激问题。我们使用聚己内酯(PCL)作为负载抗氧化剂氧化石墨烯(GO)的基础,开发了一种纳米纤维支架,并用施旺细胞脱细胞基质涂覆该生物支架。体外研究揭示了所开发的生物支架的抗氧化和髓鞘再生特性。基于这些结果,所开发的多功能生物支架方法可能是一种很有前途的治疗脱髓鞘疾病的生物材料方法。
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引用次数: 0
Enhanced anti-glioma efficacy of biodegradable periodic mesoporous organosilica nanoparticles through target delivery of chemotherapeutics 可生物降解的周期性介孔有机硅纳米粒子通过靶向递送化疗药物增强了抗神经胶质瘤的功效。
IF 4.2 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2023-10-04 DOI: 10.1007/s10856-023-06747-x
Min Dong, Ying Liu, Biao Liu, Jin Peng, Yuxia Tang, Guangming Lu, Haibin Shi, Feipeng Zhu

Glioma is the most common malignant tumor of the brain and enhancing the efficacy of chemotherapy in glioma is critical for improving patients’ prognosis. In this study, a glioma-targeting drug delivery system is constructed using biodegradable periodic mesoporous organosilica nanoparticles (PMO) that are modified with lactoferrin (Lf) ligands. The obtained PMO is doped with thioether groups and can be degraded in the high concentration of glutathione in tumor cells. The surface area and pore volume of PMO are 772 cm2/g and 0.98 cm3/g, respectively and the loading capacity of doxorubicin (Dox) is as high as 20%. The results of the confocal laser scanning microscope show that the uptake of PMO-Lf@Dox by C6 cells is higher than PMO@Dox. The quantitative analysis of the flow cytometer further demonstrates that more PMO-Lf@Dox enter C6 cells, indicating that the modification of lactoferrin can significantly increase the uptake of C6 cells. Finally, the therapeutic efficacy results show that Lf-modified PMO enhances the inhibitory effect of Dox on C6 cells when incubated for 24 h and 72 h. In summary, this lactoferrin receptor-mediated PMO drug carrier with biodegradability in glutathione in tumor cells can be used to enhance drug delivery into glioma without long-term accumulation in vivo.

胶质瘤是最常见的脑恶性肿瘤,提高胶质瘤化疗的疗效对改善患者预后至关重要。在本研究中,使用乳铁蛋白(Lf)配体修饰的可生物降解的周期性介孔有机硅纳米颗粒(PMO)构建了一个神经胶质瘤靶向药物递送系统。所获得的PMO掺杂有硫醚基团,并且可以在肿瘤细胞中的高浓度谷胱甘肽中降解。PMO的表面积和孔隙体积为772 cm2/g和0.98 并且阿霉素(Dox)的负载能力高达20%。共焦激光扫描显微镜的结果表明PMO-Lf@DoxC6细胞的PMO@Dox.流式细胞仪的定量分析进一步表明PMO-Lf@Dox进入C6细胞,表明乳铁蛋白的修饰可以显著增加C6细胞的摄取。最后,疗效结果表明,Lf修饰的PMO在孵育24小时时增强了Dox对C6细胞的抑制作用 h和72 h.总之,这种乳铁蛋白受体介导的PMO药物载体在肿瘤细胞中的谷胱甘肽中具有可生物降解性,可用于增强向神经胶质瘤的药物递送,而无需在体内长期积累。在本研究中,使用乳铁蛋白(Lf)配体修饰的周期性介孔有机硅纳米颗粒(PMO)构建了一个神经胶质瘤靶向药物递送系统。这种乳铁蛋白受体介导的PMO药物载体可用于增强向脑胶质瘤的药物递送。
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引用次数: 0
Tumor-microenvironment responsive nano-carrier system for therapy of prostate cancer 肿瘤微环境响应性纳米载体系统治疗前列腺癌症
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-21 DOI: 10.1007/s10856-023-06749-9
Lujing Li, Renjie Li, Jiachun Li, Jiyi Yao, Qingyuan Zhang, Qiao Ji, Zuofeng Xu

Poor selectivity, low bioavailability and serious systemic side-effects have limited the application of traditional chemotherapy method for treatment of prostate cancer. Stimuli-responsive drug delivery systems for chemotherapy are mainly based on the unique characteristics of tumor microenvironment. In this study, the GSH-sensitive poly-TTG-SS@DTX NPs (DTX-loaded poly-Tetraethylene glycol nanoparticles) were designed and synthesized, which were characterized with nanosized diameter (92.8 ± 2.5 nm) and negatively charged surface charge (−24.7 ± 5.56 mV). Experiments in vitro showed that poly-TTG-SS@DTX NPs had good compatibility to healthy cells and strong anti-tumor effect because of rapid and sustained drug release of DTX from poly-TTG-SS@DTX NPs under the tumor-microenvironment condition. The cellular activity remained greater than 90% when the concentration of poly-TTG-SS NPs reached as high as 100 µg/mL treated on healthy cells. The killing effect of DTX loading NPs group on C4-2 cells was stronger than that of free anti-tumor drug and free DTX combined with the blank nano-carrier (25.21% vs 19.93% vs 20.96%). In conclusion, poly-TTG-SS@DTX NPs may provide a new therapeutic strategy for the chemotherapy of prostate cancer.

Graphical Abstract

选择性差、生物利用度低、全身副作用严重,限制了传统化疗方法在癌症治疗中的应用。用于化疗的刺激反应性药物递送系统主要基于肿瘤微环境的独特特性。在本研究中,GSH敏感性poly-TTG-SS@DTX设计并合成了纳米颗粒(DTX负载的聚四乙二醇纳米颗粒),其具有纳米直径(92.8 ± 2.5 nm)和带负电的表面电荷(−24.7 ± 5.56 mV)。体外实验表明poly-TTG-SS@DTXNPs与健康细胞具有良好的相容性,并且由于DTX从poly-TTG-SS@DTX肿瘤微环境条件下的NPs。当聚TTG-SS NP的浓度高达100时,细胞活性保持大于90% µg/mL在健康细胞上处理。负载DTX的NPs组对C4-2细胞的杀伤作用强于游离抗肿瘤药物和游离DTX与空白纳米载体的联合杀伤作用(25.21%vs19.93%vs20.96%),poly-TTG-SS@DTXNP可能为癌症的化疗提供一种新的治疗策略。图形摘要
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引用次数: 0
Increased antibiofilm and growth inhibitory effect of Imipenem/Cilastatin nanoliposomes against clinical Pseudomonas aeruginosa isolates 亚胺培南/西司他丁纳米脂质体对临床铜绿假单胞菌的抗菌膜增强和生长抑制作用
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-21 DOI: 10.1007/s10856-023-06752-0
Faezeh Milani, Khosro Adibkia, Hamed Hamishehkar, Tooba Gholikhani, Farhad Bani, Morteza Milani

Numerous infections are linked to Pseudomonas aeruginosa. It is one of the major medical concerns because of virulence and antibiotic resistance. Antibiotic encapsulation in liposomes is a good strategy for controlling infections caused by this microorganism. Evaluation of anti-Pseudomonas aeruginosa effect of liposomal form of Imipenem/Cilastatin in vitro condition. By using the disk agar diffusion technique, the isolates’ pattern of antibiotic resistance was identified. The antibiotic was placed into the nanoliposome after it had been made using the thin layer and ethanol injection techniques. SEM and DLS were used to determine the size, shape, and zeta potential of the encapsulated drug form and the empty nanoliposome. Additionally, Imipenem/Cilastatin encapsulation in nanoliposomes was studied using FT-IR spectroscopy. In the microbial assay experiments the MIC, MBC and MBEC of liposomal and free drug forms were determined. The nanoparticles were spherical, with a diameter ranging from 30 to 39 nm, and the EE% in the thin layer and ethanol injection procedures were 97 and 98, respectively. Imipenem/Cilastatin nanoliposomes showed peaks at 3009 cm−1 and 1650 cm−1, demonstrating the thermodynamic stability for the chemical structure of the drug enclosed and validating the encapsulation of antibiotic in the nanoliposomes. When compared to free drug forms, nanoliposomes had lower MIC and MBC values in the majority of the isolates and had a greater ability to eradicate the biofilm formation. It was shown that the two nanoliposome preparation techniques were more efficient in 80% of the isolates, which had outcomes that were consistent with those of numerous other investigations. Overall, we demonstrated that the antibacterial activity of nanoliposomes was higher than that of the free drug form based on the evaluation of their MIC and MBC. Pharmaceutical nanoliposome techniques provide an excellent future perspective on how to manage microbial infections that are resistant to antibiotics.

Graphical Abstract

许多感染与铜绿假单胞菌有关。由于毒力和抗生素耐药性,它是主要的医学问题之一。脂质体中的抗生素包封是控制由这种微生物引起的感染的良好策略。亚胺培南/西司他丁脂质体抗铜绿假单胞菌作用的体外评价。采用琼脂扩散法对分离株进行了耐药性鉴定。在使用薄层和乙醇注射技术制成纳米脂质体后,将抗生素放入纳米脂质体中。使用SEM和DLS来确定包封的药物形式和空的纳米脂质体的尺寸、形状和ζ电位。此外,利用FT-IR光谱研究了亚胺培南/西司他丁在纳米脂质体中的包封。在微生物测定实验中,测定了脂质体和游离药物形式的MIC、MBC和MBEC。纳米颗粒是球形的,直径从30到39 nm,并且薄层和乙醇注射程序中的EE%分别为97和98。亚胺培南/西司他丁纳米脂质体在3009处显示峰值 cm−1和1650 cm−1,证明了包封药物化学结构的热力学稳定性,并验证了抗生素在纳米脂质体中的包封。与游离药物形式相比,纳米脂质体在大多数分离物中具有较低的MIC和MBC值,并且具有更大的根除生物膜形成的能力。研究表明,这两种纳米脂质体制备技术在80%的分离株中更有效,其结果与许多其他研究的结果一致。总体而言,基于对其MIC和MBC的评估,我们证明纳米脂质体的抗菌活性高于游离药物形式。药物纳米脂质体技术为如何管理对抗生素具有耐药性的微生物感染提供了一个极好的未来前景。图形摘要
{"title":"Increased antibiofilm and growth inhibitory effect of Imipenem/Cilastatin nanoliposomes against clinical Pseudomonas aeruginosa isolates","authors":"Faezeh Milani,&nbsp;Khosro Adibkia,&nbsp;Hamed Hamishehkar,&nbsp;Tooba Gholikhani,&nbsp;Farhad Bani,&nbsp;Morteza Milani","doi":"10.1007/s10856-023-06752-0","DOIUrl":"10.1007/s10856-023-06752-0","url":null,"abstract":"<div><p>Numerous infections are linked to <i>Pseudomonas aeruginosa</i>. It is one of the major medical concerns because of virulence and antibiotic resistance. Antibiotic encapsulation in liposomes is a good strategy for controlling infections caused by this microorganism. Evaluation of anti-<i>Pseudomonas aeruginosa</i> effect of liposomal form of Imipenem/Cilastatin in vitro condition. By using the disk agar diffusion technique, the isolates’ pattern of antibiotic resistance was identified. The antibiotic was placed into the nanoliposome after it had been made using the thin layer and ethanol injection techniques. SEM and DLS were used to determine the size, shape, and zeta potential of the encapsulated drug form and the empty nanoliposome. Additionally, Imipenem/Cilastatin encapsulation in nanoliposomes was studied using FT-IR spectroscopy. In the microbial assay experiments the MIC, MBC and MBEC of liposomal and free drug forms were determined. The nanoparticles were spherical, with a diameter ranging from 30 to 39 nm, and the EE% in the thin layer and ethanol injection procedures were 97 and 98, respectively. Imipenem/Cilastatin nanoliposomes showed peaks at 3009 cm<sup>−1</sup> and 1650 cm<sup>−1</sup>, demonstrating the thermodynamic stability for the chemical structure of the drug enclosed and validating the encapsulation of antibiotic in the nanoliposomes. When compared to free drug forms, nanoliposomes had lower MIC and MBC values in the majority of the isolates and had a greater ability to eradicate the biofilm formation. It was shown that the two nanoliposome preparation techniques were more efficient in 80% of the isolates, which had outcomes that were consistent with those of numerous other investigations. Overall, we demonstrated that the antibacterial activity of nanoliposomes was higher than that of the free drug form based on the evaluation of their MIC and MBC. Pharmaceutical nanoliposome techniques provide an excellent future perspective on how to manage microbial infections that are resistant to antibiotics.</p><h3>Graphical Abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":647,"journal":{"name":"Journal of Materials Science: Materials in Medicine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10856-023-06752-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41080066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
L-serine combined with carboxymethyl chitosan guides amorphous calcium phosphate to remineralize enamel L-丝氨酸与羧甲基壳聚糖结合引导无定形磷酸钙对牙釉质进行再矿化。
IF 4.2 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2023-09-02 DOI: 10.1007/s10856-023-06745-z
Yinghui Wang, Shuting Zhang, Peiwen Liu, Fan Li, Xu Chen, Haorong Wang, Zhangyi Li, Xi Zhang, Xiangyu Zhang, Xu Zhang

The aim of this study is to investigate a robust and stable calcium-phosphorus system to remineralize human early enamel caries lesions with nanocomplexes of carboxymethyl chitosan/L-serine/amorphous calcium phosphate (CMC-Ser-ACP) to develop an effective method for mimicking the amelogenin (AMEL) mineralization pattern through ACP assembly. A CMC-Ser-ACP nanocomplex solution was first synthesized by a chemical precipitation method, and then 1% sodium hypochlorite (NaClO) was added to induce ACP phase formation. The morphologies of the nanocomplexes were characterized by transmission electron microscopy (TEM), and zeta potential analysis and Fourier transform infrared spectroscopy (FTIR) were performed to detect surface charge and functional group changes. The subtle changes of the demineralized enamel models induced by the remineralization effect were observed by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The CMC-Ser-ACP nanocomplex solution could be preserved without any precipitation for 45 days. After the application of NaClO and through the guidance of Ser, ACP nanoparticles transformed into relatively orderly arranged hydroxyapatite (HAP) crystals, generating an aprismatic enamel-like layer closely integrated with the demineralized enamel, which resulted in enhanced mechanical properties for the treatment of early enamel caries lesions. The CMC-Ser-ACP nanocomplex solution is a remineralization system with great solution stability, and when NaClO is added, it can rapidly regenerate an aprismatic enamel-like layer in situ on the demineralized enamel surface. This novel remineralization system has stable chemical properties and can greatly increase the therapeutic effects against early enamel caries.

Graphical Abstract

本研究的目的是用羧甲基壳聚糖/L-丝氨酸/无定形磷酸钙纳米复合物(CMC Ser-ACP)研究一种坚固稳定的钙磷系统来再矿化人类早期釉质龋损伤,以开发一种通过ACP组装模拟釉原蛋白(AMEL)矿化模式的有效方法。首先通过化学沉淀法合成了CMC-Ser-ACP纳米复合物溶液,然后加入1%的次氯酸钠(NaClO)以诱导ACP相的形成。通过透射电子显微镜(TEM)对纳米复合物的形貌进行了表征,并进行了ζ电位分析和傅里叶变换红外光谱(FTIR)来检测表面电荷和官能团的变化。通过扫描电子显微镜(SEM)和X射线衍射(XRD)观察了再矿化效应引起的脱矿釉质模型的细微变化。CMC Ser-ACP纳米复合物溶液可以在没有任何沉淀的情况下保存45天。应用NaClO后,在Ser的引导下,ACP纳米颗粒转化为排列相对有序的羟基磷灰石(HAP)晶体,产生与脱矿釉质紧密结合的杏仁状釉质层,从而提高了治疗早期釉质龋损伤的力学性能。CMC-Ser-ACP纳米复合物溶液是一种具有良好溶液稳定性的再矿化系统,当加入NaClO时,它可以在脱矿牙釉质表面原位快速再生一层杏仁状牙釉质层。这种新型的再矿化系统具有稳定的化学性质,可以大大提高对早期釉质龋的治疗效果。
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引用次数: 0
Targeted delivery of a short antimicrobial peptide (CM11) against Helicobacter pylori gastric infection using concanavalin A-coated chitosan nanoparticles 使用刀豆蛋白a包被的壳聚糖纳米颗粒靶向递送抗幽门螺杆菌胃感染的短抗菌肽(CM11)。
IF 4.2 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2023-08-31 DOI: 10.1007/s10856-023-06748-w
Mehrdad Moosazadeh Moghaddam, Shahin Bolouri, Reza Golmohammadi, Mahdi Fasihi-Ramandi, Mohammad Heiat, Reza Mirnejad

Helicobacter pylori is the cause of most cases of stomach ulcers and also causes some digestive cancers. The emergence and spread of antibiotic-resistant strains of H. pylori is one of the most important challenges in the treatment of its infections. The present study aims to develop a concanavalin A (ConA) coated chitosan (CS) nanocarrier-based drug delivery for the targeted release of peptides to the site of H. pylori infection. Accordingly, chitosan was used as an encapsulating agent for CM11 peptide delivery by applying ionotropic gelation method. Con-A was used for coating CS nanoparticles to target H. pylori. The CS NPs and ConA-CS NPs were characterized by FTIR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). The MIC of CM11-loaded ConA-CS NPs against H. pylori SS1 strain was analyzed in vitro. In order to evaluate the treatment efficiency in vivo, a gastric infection model of H. pylori SS1 strain was established in mice and histopathological studies and IL-1β cytokine assay were performed. Based on the results, the size frequency for CS NPs and ConA-CS NPs was about 200 and 350 nm, respectively. The prepared CM11-loaded ConA-CS NPs exhibited antibacterial activity against H. pylori SS1 strain with a concentration of 32 µg/ml. The highest healing process was observed in synthesized CM11-loaded ConA-CS NPs treatments and a significant decrease in IL-1β was observed. Our findings highlight the potential of chitosan nanoparticles as a drug delivery vehicle in the treatment of gastric infection model of H. pylori SS1 strain.

Graphical Abstract

幽门螺杆菌是大多数胃溃疡的病因,也会导致一些消化道癌症。幽门螺杆菌抗生素耐药性菌株的出现和传播是治疗其感染的最重要挑战之一。本研究旨在开发一种基于刀豆球蛋白a(ConA)包被的壳聚糖(CS)纳米载体的药物递送,用于将肽靶向释放到幽门螺杆菌感染部位。因此,采用离子凝胶法将壳聚糖用作CM11肽递送的包封剂。Con-A用于包覆CS纳米颗粒以靶向幽门螺杆菌。通过FTIR、动态光散射(DLS)和扫描电子显微镜(SEM)对CS NPs和ConA CS NPs进行了表征。在体外分析了CM11负载的ConA-CS NPs对幽门螺杆菌SS1菌株的MIC。为了评价体内治疗效果,在小鼠中建立了幽门螺杆菌SS1菌株的胃感染模型,并进行了组织病理学研究和IL-1β细胞因子测定。根据结果,CS NP和ConA CS NP的尺寸频率分别约为200和350 nm。所制备的负载CM11的ConA-CS NP对浓度为32的幽门螺杆菌SS1菌株表现出抗菌活性 µg/ml。在合成的CM11负载的ConA-CS NPs治疗中观察到最高的愈合过程,并且观察到IL-1β的显著降低。我们的研究结果强调了壳聚糖纳米粒子作为药物递送载体在治疗幽门螺杆菌SS1菌株胃感染模型中的潜力。
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引用次数: 0
Enhanced therapeutic effects of mesenchymal stem cell-derived extracellular vesicles within chitosan hydrogel in the treatment of diabetic foot ulcers 壳聚糖水凝胶增强间充质干细胞来源的细胞外囊泡治疗糖尿病足溃疡的疗效
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-28 DOI: 10.1007/s10856-023-06746-y
Shuangshuang Yang, Siyu Chen, Chengpeng Zhang, Jing Han, Chunyuan Lin, Xiaohui Zhao, Huizhen Guo, Yi Tan

Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising candidates for cell-free therapy in various diseases, including chronic cutaneous wounds. However, the lack of standardized protocols for EVs’ preparation and identification poses a significant challenge to their clinical application. Thus, the objective was to develop a safe and efficient method for the large-scale production of hUCMSC-derived EVs while establishing a comprehensive identification protocol encompassing morphology, particle size distribution, protein expression, and purity. This study observed that most of the EVs acquired through the protocol exhibited either a cup-shaped or round-shaped structure, with a median diameter of ~73.25?nm. The proportions of EVs positive for CD9, CD63, and CD81 were 37.5%, 38.6%, and 19.8%, respectively. To enhance their therapeutic potential in wound treatment, EVs were incorporated into chitosan hydrogel, forming chitosan hydrogel-EVs (CS-EVs). Furthermore, it was demonstrated that CS-EVs exhibited continuous release of EVs into the surrounding environment and, importantly, that the released EVs were internalized by human umbilical vein endothelial cells (HUVECs), resulting in significant enhancement of cell migration and angiogenesis. Additionally, in a rat model of diabetic foot ulcers, CS-EVs demonstrated a robust therapeutic effect in promoting wound healing. Following a 15-day treatment period, the group treated with CS-EVs demonstrated an impressive 93.3% wound closure ability, accompanied by a high degree of re-epithelialization. In contrast, the control group exhibited only a 71.5% reduction in wound size. In summary, this study offers solutions for the purification, characterization, and application of EVs in clinical wound treatment. These results not only offer fresh perspectives on the involvement of hUCMSC-derived EVs in wound healing but also introduce a non-invasive approach for applying EVs that holds practical significance in skin repair.

Graphical Abstract

来源于人脐带间充质干细胞(hUCMSCs)的细胞外囊泡(EVs)已成为各种疾病(包括慢性皮肤伤口)无细胞治疗的有希望的候选者。然而,电动汽车的制备和鉴定缺乏标准化的方案,这对其临床应用构成了重大挑战。因此,我们的目标是开发一种安全有效的方法来大规模生产humcc衍生的电动汽车,同时建立一个全面的鉴定方案,包括形态、粒度分布、蛋白质表达和纯度。研究发现,通过该方案获得的大多数ev呈杯状或圆形结构,中位直径约为73.25 nm。CD9、CD63和CD81的阳性率分别为37.5%、38.6%和19.8%。为了提高ev在创面治疗中的应用潜力,我们将其掺入壳聚糖水凝胶中,形成壳聚糖水凝胶- ev (cs - ev)。此外,研究表明,cs - ev能够将ev持续释放到周围环境中,重要的是,释放的ev被人脐静脉内皮细胞(HUVECs)内化,从而显著增强细胞迁移和血管生成。此外,在糖尿病足溃疡大鼠模型中,cs - ev在促进伤口愈合方面表现出强大的治疗作用。经过15天的治疗期,cs - ev治疗组显示出令人印象深刻的93.3%的伤口愈合能力,并伴有高度的再上皮化。相比之下,对照组的伤口大小仅减少了71.5%。综上所述,本研究为ev的纯化、表征和在临床伤口治疗中的应用提供了解决方案。这些结果不仅为humcc衍生的ev参与伤口愈合提供了新的视角,而且为ev在皮肤修复中具有实际意义的应用提供了一种非侵入性方法。图形抽象
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引用次数: 0
Cobalt-containing borate bioactive glass fibers for treatment of diabetic wound 治疗糖尿病伤口的含钴硼酸盐生物活性玻璃纤维
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-02 DOI: 10.1007/s10856-023-06741-3
Minhui Zhang, Aihua Yao, Fanrong Ai, Jian Lin, Qingge Fu, Deping Wang

Impaired angiogenesis is one of the predominant reasons for non-healing diabetic wounds. Cobalt is well known for its capacity to induce angiogenesis by stabilizing hypoxia-inducible factor-1α (HIF-1α) and subsequently inducing the production of vascular endothelial growth factor (VEGF). In this study, Co-containing borate bioactive glasses and their derived fibers were fabricated by partially replacing CaO in 1393B3 borate glass with CoO. Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) analyses were performed to characterize the effect of Co incorporation on the glass structure, and the results showed that the substitution promoted the transformation of [BO3] into [BO4] units, which endow the glass with higher chemical durability and lower reaction rate with the simulated body fluid (SBF), thereby achieving sustained and controlled Co2+ ion release. In vitro biological assays were performed to assess the angiogenic potential of the Co-containing borate glass fibers. It was found that the released Co2+ ion significantly enhanced the proliferation, migration and tube formation of the Human Umbilical Vein Endothelial Cells (HUVECs) by upregulating the expression of angiogenesis-related proteins such as HIF-1α and VEGF. Finally. In vivo results demonstrated that the Co-containing fibers accelerated full-thickness skin wound healing in streptozotocin (STZ)-induced diabetic rat model by promoting angiogenesis and re-epithelialization.

Graphical Abstract

血管生成障碍是糖尿病创面不愈合的主要原因之一。众所周知,钴通过稳定缺氧诱导因子-1α (HIF-1α)并随后诱导血管内皮生长因子(VEGF)的产生来诱导血管生成。在本研究中,用CoO部分取代1393B3硼酸玻璃中的CaO,制备了含钴硼酸生物活性玻璃及其衍生纤维。傅里叶变换红外光谱(FTIR)和核磁共振(NMR)分析表征了Co加入对玻璃结构的影响,结果表明Co的加入促进了[BO3]向[BO4]单元的转化,使玻璃具有更高的化学耐久性和较低的与模拟体液(SBF)的反应速率,从而实现了Co2+离子的持续和可控释放。体外生物实验评估含钴硼酸玻璃纤维的血管生成潜能。研究发现,释放的Co2+离子通过上调HIF-1α和VEGF等血管生成相关蛋白的表达,显著促进人脐静脉内皮细胞(HUVECs)的增殖、迁移和成管。最后。体内实验结果表明,含钴纤维通过促进血管生成和再上皮化,促进链脲佐菌素(STZ)诱导的糖尿病大鼠模型全层皮肤创面愈合。图形抽象
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引用次数: 0
Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer 靶向载药PLGA-PCL微球用于特异性和局部治疗三阴性乳腺癌
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-02 DOI: 10.1007/s10856-023-06738-y
Chukwudalu C. Nwazojie, John D. Obayemi, Ali A. Salifu, Sandra M. Borbor-Sawyer, Vanessa O. Uzonwanne, Chinyerem E. Onyekanne, Udom M. Akpan, Killian C. Onwudiwe, Josephine C. Oparah, Olushola S. Odusanya, Winston O. Soboyejo

The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with detailed thermodynamically driven drug release kinetics, over a period of three months using encapsulated targeted drugs (prodigiosin-EphA2 or paclitaxel-EphA2) and control drugs [Prodigiosin (PGS), and paclitaxel (PTX)] were studied. Results from in vitro study showed a sustained and localized drug release that is well-characterized by non-Fickian Korsmeyer–Peppas kinetics model over the range of temperatures of 37 °C (body temperature), 41 °C, and 44 °C (hyperthermic temperatures). The in vitro alamar blue, and flow cytometry assays in the presence of the different drug-loaded polymer formulations resulted to cell death and cytotoxicity that was evidence through cell inhibition and late apoptosis on triple negative breast cancer (TNBC) cells (MDA-MB 231). In vivo studies carried out on groups of 4-week-old athymic nude mice that were induced with subcutaneous TNBC, showed that the localized release of the EphA2-conjugated drugs was effective in complete elimination of residual tumor after local surgical resection. Finally, ex vivo histopathological analysis carried out on the euthanized mice revealed no cytotoxicity and absence of breast cancer metastases in the liver, kidney, and lungs 12 weeks after treatment. The implications of the results are then discussed for the development of encapsulated EphA2-conjugated drugs formulation in the specific targeting, localized, and sustain drug release for the elimination of local recurred TNBC tumors after surgical resection.

Graphical Abstract

本文介绍了由聚乳酸-羟基乙酸-聚己内酯共混聚合物(PLGA-PCL)制备的靶向载药聚合物微球用于靶向和局部肿瘤药物递送的实验和分析研究结果。在三个月的时间里,研究了包封的靶向药物(Prodigiosin - epha2或paclitaxel- epha2)和对照药物(Prodigiosin (PGS)和paclitaxel (PTX))的体外缓释动力学。体外研究结果显示,在37°C(体温)、41°C和44°C(高温)的温度范围内,非菲氏Korsmeyer-Peppas动力学模型很好地表征了药物的持续和局部释放。体外alamar blue和流式细胞术检测显示,不同的载药聚合物配方会导致细胞死亡和细胞毒性,这一点通过三阴性乳腺癌(TNBC)细胞的细胞抑制和晚期凋亡得到了证明(MDA-MB 231)。对皮下TNBC诱导的4周龄胸腺裸小鼠进行的体内研究表明,局部手术切除后,epha2偶联药物的局部释放可以有效地完全消除残留肿瘤。最后,对安乐死小鼠进行的离体组织病理学分析显示,治疗12周后,没有细胞毒性,肝脏、肾脏和肺部没有乳腺癌转移。然后讨论了研究结果对开发epha2缀合的囊化药物制剂的意义,该制剂具有特异性靶向、局部和持续释放药物的功能,以消除手术切除后局部复发的TNBC肿瘤。图形抽象
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引用次数: 0
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Journal of Materials Science: Materials in Medicine
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