Hypoxia poses a significant challenge to the efficacy of photodynamic therapy (PDT) for cancer treatment. This study aims to design and synthesize PEGylated liposomes encapsulating MnO₂, indocyanine green (ICG), and H-chain ferritin (HFn) to potentially address hypoxia and enhance the therapeutic outcomes of PDT. PEGylated liposomes (ICG/MnO₂-HFn-mPEG-DSPE-Lip) were constructed with a rod-like structure, incorporating MnO₂ as a hypoxia-modulating agent and ICG as a photosensitizer. The drug loading capacity, stability and safety of liposomes were characterized. Singlet oxygen quantum yield (ΦΔ) was measured under simulated tumor microenvironment conditions. In vitro phototoxicity was evaluated using A549 human lung adenocarcinoma cells. Liposomes have a high drug loading capacity, good biocompatibility and good long-term stability. Under tumor-simulated conditions, ΦΔ was significantly improved, increasing from 0.210 for free ICG to 0.507. The liposomes demonstrated remarkable phototoxic effects on A549 cells (90.5
Drug delivery systems utilizing tumor targeting, microenvironment responsiveness, and combination therapy have demonstrated advantages in antitumor research by enhancing efficacy and reducing side effects. In this study, a bifunctional amphiphilic carrier material (HA-SSS-MC) with targeting and glutathione-responsive properties was developed by linking hydrophilic hyaluronic acid (HA) and hydrophobic methyl cholate (MC) via a trisulfide bond. The photosensitizer zinc phthalocyanine (ZnPc) and the chemotherapeutic drug 5-fluorouracil (5-FU) were encapsulated within the amphiphiles to form dual drug-loaded nanomicelles (HA-SSS-MC/5-FU/ZnPc). These nanomicelles exhibited high drug loading efficiency, stability, and glutathione (GSH)-sensitive release properties. Notably, the singlet oxygen quantum yield of the drug-loaded nanomicelles was significantly higher than that of the free photosensitizer under high glutathione conditions. In vitro cellular assays confirmed that HA-SSS-MC/5-FU/ZnPc nanomicelles exhibited low cytotoxicity and demonstrated a significant cancer cell-killing effect, surpassing Free 5-FU or ZnPc alone. Furthermore, the nanomicelles showed targeting capabilities and accumulated within endosomes. In A549 tumor-bearing mice, HA-SSS-MC/5-FU/ZnPc exhibited the strongest antitumor efficacy and the lowest toxicity compared to all other groups. In conclusion, the targeted GSH-responsive dual drug-carrying nanomicelles will be a promising strategy for cancer therapy.
Combination therapy and the drug delivery in response to the tumor microenvironment can effectively improve the efficacy of anticancer therapy. Polymeric nanoparticles can increase the solubility of water-insoluble drugs and have been evaluated as carriers for anti-cancer drugs in several clinical trials. In this paper, zinc phthalocyanine-encapsulated with a boronate-linked polydopamine-poloxamers 407 nanoparticles were developed for pH response and reactive oxygen species (ROS) response release, as well as synergistic photothermal and photodynamic effects. These nanoparticles exhibited a favorable size of 75.02 & PLUSMN; 1.12 nm, stability within 28 days, pH and ROS release up to 57.29% within 84 h, and 73.5% inhibition of A549 cells at a concentration of 5 & mu;g/mL. Overall, our work provides an effective strategy for the encapsulation of hydrophobic photosensitizers, combined PDT and PTT therapy.
Photodynamic therapy (PDT) has emerged as a non-invasive modality where photosensitizer (PS) plays an indispensable role for treating tumors. This study proposes a novel Zein nanoparticle (ZP) encapsulating Zinc phthalocyanine (ZnPc) that targets tumor through intravenous delivery. The ZPs were prepared by phase separation process. Modification of ZPs were realized through encapsulation of polydopamine (PDA) and hyaluronic acid (HA) in order to maintain photothermal, pH-responsive, and tumor-targeting properties. The physiochemical properties, in vitro release, and in vitro evaluation of photothermal and photodynamic effects were studied. The biosafety was analyzed through cytotoxicity assay using human lung cancer cell line A549 as model. The excellent biosafety and significant anti-tumor effect demonstrated that the novel ZPs can be potential candidates for the alternative treatment of cancer.
[目的]制备三乙酸甘油酯滤棒基体标准物质,可解决实验室能力验证无准确对照品的问题,同时也可应用于近红外法测定滤棒中的三乙酸甘油酯建模样品的赋值以及近红外设备的期间核查等.[方法]通过严格控制滤棒生产条件,制备三乙酸甘油酯滤棒基体标准物质,进行均匀性检验、稳定性考察和联合定值.[结果](1)6 个实验室对该标准物质的合作定值结果为 8.50%;(2)在 95%的置信概率下,取扩展因子k=2,则扩展不确定度为 0.24%.[结论]该标准物质符合国家二级标准物质的技术要求,可满足近红外法赋值和实验室能力验证、数据比对的需要.
宫颈癌的发生与人乳头瘤病毒(HPV)感染密切相关.治疗HPV感染可有效预防宫颈癌.洛匹那韦(LPV)是Food and Drug Administration(FDA)批准的抗艾滋病病毒的治疗药物,研究发现洛匹那韦具有抗HPV病毒的活性.本工作旨在制备一种负载LPV的纳米胶束复合水凝胶载药系统,探究其通过阴道黏膜局部给药的性能.采用两亲性聚合物维生素E聚乙二醇琥珀酸酯(TPGS)和助渗透剂牛磺脱氧胆酸钠(STDC)自组装制备混合载药胶束(TPGS-STDC/LPV),混合胶束分散在温敏凝胶中形成载药纳米胶束复合温敏水凝胶(NMCH).对TPGS-STDC/LPV的粒径、ZETA电位、形貌、包封率、载药量和释药等进行了检测,还测试了NMCH的黏膜粘附性、药物释放、透皮渗透和抗病毒活性等.实验结果表明,TPGS-STDC/LPV具有高药物包封率、高载药量,累积释放率达(96.82±2.93)%(pH=4.5,72h),表现出酸响应释放性能;复合水凝胶具有适宜人体的温敏特性,对阴道上皮黏膜具有优异的粘附性,所制备的NMCH的LPV渗透率最好,为(54.05±2.74)%,约为游离LPV的7.4倍;NMCH具有显著的抗HPV病毒活性.该体系适合用于阴道局部给药.
[目的]基于卷烟烟气粒相物滤片的近红外光谱,快速测定卷烟烟气中烟碱、焦油和一氧化碳释放量.[方法]利用傅里叶变换近红外光谱仪采集捕集了卷烟烟气粒相物的剑桥滤片近红外光谱,采用传统方法测定烟碱、焦油和一氧化碳含量,通过化学计量学算法剔除异常样品并对光谱进行预处理,从而建立了卷烟烟气中烟碱、焦油和一氧化碳的近红外定量分析模型.[结果]所建的焦油、烟碱和一氧化碳模型决定系数(R2)分别为0.944、0.948和0.922,均方预测残差(RMSECV)分别为0.024、0.323和0.648.外部验证结果显示与传统方法对比无显著差异.[结论]该方法快速、高效、无污染,为卷烟烟气中烟碱、焦油和一氧化碳释放量检测提供了一种新方法.
基于近红外光谱法建立了快速预测烟用料液中水溶性总糖和还原糖含量的模型,用以评价烟用料液配制质量的稳定性.以连续流动法为参比,测定5个不同品牌120个料液样品中总糖和还原糖的含量;以近红外光谱仪分析样品,采用二阶导数和Norris滤波平滑对原始近红外光谱进行预处理,在5400~7600 cm-1和4000~4600 cm-1波段内用偏最小二乘法建立总糖和还原糖的定量分析模型.结果显示:当主因子数为6时,总糖定量分析模型的校正相关系数(Rc)为0.9985、预测相关系数(Rp)为0.9981、交互验证相关系数(Rcv)为0.9988、校正均方根误差(RMSEC)为0.257、预测均方根误差(RMSEP)为0.261、交互验证均方根误差(RMSECV)为0.284;还原糖定量分析模型的Rc为0.9990、Rp为0.9987、Rcv为0.9992、RMSEC为0.235、RMSEP为0.250、RMSECV为0.266.经配对T检验统计学分析,本法与连续流动法对料液样品中水溶性糖含量的测定不存在显著性差异.利用建立的模型对112个待检烟用料液样品中水溶性糖含量进行预测,运用统计过程控制技术中的3σ过程控制原理判断待检烟用料液配制质量的稳定性,并根据样品的理化指标来验证结果的准确度.结果表明,A品牌5,14,28号样品和C品牌21号样品均不属于正常样品,B、D和E品牌样品中水溶性糖含量均在质量控制范围内,说明样品配制质量的稳定性较好.
二氧化锰(MnO2)纳米片作为一种层状过渡金属二氧化物纳米材料,因其具有较大比表面积、强光学吸收和氧化能力、高的催化活性和优良的力学性能等优点,近年来在生物传感和生物医学领域的应用研究广泛.本文简单概述了 MnO2纳米片的纳米结构和性质,详细介绍了它们在生物传感、生物成像及癌症治疗中的应用,最后展望了 MnO2纳米片在未来的发展前景和面临的挑战.
目的:采用双乳化溶剂蒸发法,优化无籽刺梨多糖纳米粒制备工艺,并对其进行表征.方法:采用响应面法以内水相W1和有机相O的比例、初级乳PE和外水相W2的比例以及泊洛沙姆P188的浓度为自变量,纳米粒的包封率为响应值,对制备工艺进行优化.结果:最佳制备工艺为W1和O的比例为1:8,PE和W2的比例为1:7,泊洛沙姆P188的浓度为0.1%(W/V).该条件下制备的纳米粒粒径为219.14±2.67 nm,多分散系数为0.103±0.001,Zeta电位为-17.2±1.76 mV,包封率为95.08±0.90%,载药量为11.11±0.25%.透射电镜观察其呈均匀分布的球形,且表面光滑.结论:采用双乳化溶剂蒸发法制备的无籽刺梨多糖纳米粒包封率高、均匀圆整,为无籽刺梨多糖制剂的研发提供实验基础.
为探明烟叶醇化过程中代谢物和脂质的变化规律,本研究采用气相色谱-质谱联用仪(GC-MS)和液相色谱-质谱联用仪(LC-MS)相结合的方法对不同产地烟叶醇化过程中的化学成分进行了代谢组学和脂质组学分析.结果表明,醇化后的烟叶中糖类、氨基酸、脂质和核苷酸等初级代谢产物的相对含量减少,黄酮类、苯衍生物、酚类和萜类化合物等次级代谢产物则增加;进一步研究发现,上述初级代谢产物的变化随醇化时间(1~7年)的增加而递减,而次级代谢产物呈现逐年递增的趋势.同一品种云烟87(YY87)在不同产地(广东和湖南)之间化学成分差异较大,主要为氨基酸和膜脂,而醇化后差异减小.综上所述,代谢组学和脂质组学方法能有效区分醇化和非醇化烟叶,并且能揭示不同醇化程度烟叶的特征及不同产地对烟叶化学成分的影响.
A novel amphiphilic polymer with the trisulfide bond was developed. The nano-micelles could be formed through the self-assembling of this polymer with hydrophobic zinc naphthalocyanine, a NIR-absorbing photosensitizer. The micelles showed unique rods, high drug loading, high stability, high sensitivity to GSH, and excellent biosafety. The singlet oxygen production quantum yield of micelles was obviously higher than that of free photosensitizers and micelles containing disulphide bonds in the simulated tumor environment. The phototoxicity of micelles in cancer cells was significant. The redox response drug-loaded micelle was promising to enhance the photodynamic efficacy of zinc naphthalocyanine in cancer cells.
雪松醇(Cedrol,CE),是一种用途极为广泛的天然倍半萜醇,广泛存在于柏科、杉科及松科等多种植物的挥发油中.研究报道CE存在多种药理作用,包括抗炎镇痛、对心脑血管系统作用、抗肿瘤、促进头发生长、抗菌、抗疟原虫活性等.为拓宽其应用,加速其新药研发进程,有必要对其研究进行总结.通过查阅相关文献,归纳总结了CE的提取与检测以及其在合成中的应用,探讨了近年来CE的药理作用及其可能的作用机制,并分析了未来发展方向,为其应用以及新药研发提供参考.
为改善雪松醇水溶性,研究制备了雪松醇纳米乳(Cedrol Nanoemulsion,CE-NE),优化其配方,并对其理化性质进行考察.本研究采用低能乳化法制备纳米乳,在伪三元相图筛选配方的基础上,以粒径及多分散系数(polydispersity,PDI)作为评价指标,利用单形网格设计法(Simplex Lattice Design,SLD)进一步优化纳米乳配方.利用透射电镜观察最优配方纳米乳的形貌,利用粒度仪测定纳米乳粒径及Zeta电位,并考察pH以及离心稳定性等理化性质.结果表明CE-NE最优处方组成为:1.2g蓖麻油聚氧乙烯醚、0.2g肉豆蔻酸异丙酯、0.6g聚乙二醇400、2.0g水,优化得到的纳米乳透射电镜观察其形貌呈大小均一球形,粒径为16.66nm、多分散系数为0.087、Zeta电位为-6.14mV,具有良好的离心稳定性.本研究成功的制备了雪松醇纳米乳,且具有良好的理化性质,为纳米乳载体的进一步应用奠定了基础.
以无籽刺梨果实为原料,采用热水浸提法提取多糖.在单因素试验的基础上通过响应面对提取工艺条件优化,并进一步研究了其抗氧化活性.结果表明,无籽刺梨多糖提取工艺参数以浸提温度80℃、料液比30∶1 mL//g、浸提时间3h为宜,实际多糖提取率8.37%.无籽刺梨多糖具有较好的抗氧化活性和一定的还原能力,对DPPH·和·OH清除的半抑制质量浓度(IC50)分别为1.02mg/mL和0.5 mg/mL.
研究SiO2固载离子液体修饰的磁性纳米粒子(Fe3O4@SiO2@IL)制备,及其H2O2酶活性测试.结果表明,Fe3O4@SiO2@IL具有比辣根过氧化物酶更高的催化活性,并能催化H2O2与过氧化物酶底物3,3',5,5'-四甲基联苯胺形成蓝色产物.因此,开发H2O2比色检测方法,线性范围为4~100μmol/L,检出限为0.698 μmol/L.该方法还可用于葡萄糖的高灵敏度和选择性检测,线性范围为8~200μmol/L,检出限为2.39 μmol/L.将该方法用于检测实际样品(如牛奶)中的H2O2,加标回收率为94.0%~107.8%,相对标准偏差为2.24%~3.12%,准确度和精密度较高.具有过氧化物酶活性的Fe3O4@SiO2@IL纳米材料在临床诊断、制药、食品研究等领域具有潜在的应用价值.
为了研究不同三醋酸甘油酯施加量对细支爆珠滤棒物理性质及卷烟主流烟气有害成分释放量的影响,在其他条件不变的情况下,对不同三醋酸甘油酯施加量的细支爆珠滤棒的吸阻、硬度、圆周等物理性质进行了研究,并比较了不同三醋酸甘油酯施加量的细支爆珠滤棒所卷制的卷烟主流烟气有害成分释放量.结果表明:细支爆珠滤棒重量、吸阻、硬度与三醋酸甘油酯施加量呈正相关,相关系数分别为0.999、0.923和0.863.对于不同三醋酸甘油酯施加量的细支爆珠滤棒,添加爆珠会使滤棒圆周、圆度、吸阻和硬度分别平均增加0.01 mm、0.02 mm、455.50 Pa和0.22百分点,但不会影响三醋酸甘油酯的施加.细支爆珠卷烟主流烟气中苯酚释放量与三醋酸甘油酯施加量呈负相关,当三醋酸甘油酯施加量为12~42 mg/支时,三醋酸甘油酯施加量每增加10 mg/支,细支爆珠卷烟主流烟气中苯酚释放量就下降0.54μg/支.
为实现对卷烟品牌的快速识别,基于烟丝的近红外光谱数据,结合机器学习技术,以贵州中烟工业有限责任公司生产的10种品牌卷烟为对象,建立了一种卷烟品牌识别模型,并以正确识别率(Recognition Accuracy,RA)为评价指标对模型的各项关键参数进行迭代优化.利用采集的卷烟样品数据对模型进行验证,结果表明:采用连续小波变换(CWT)方法进行光谱数据预处理,概率主成分分析(PPCA)方法进行数据降维,选择Linear作为核函数,基于支持向量机(SVM)方法建立的识别模型,最高RA值达到97.20%,表明利用烟丝光谱数据可以实现对卷烟品牌的准确识别.该技术可为卷烟配方维护提供支持.
为准确识别卷烟爆珠生产中产生的拖尾缺陷并计量拖尾高度,提出了一种基于球体多角度外轮廓圆投影的拖尾缺陷检测方法.首先,通过自旋转机构和相机快速采集单颗爆珠10个不同角度的图像;其次,使用轮廓提取算法提取每张图像中爆珠外轮廓;然后,使用轮廓圆投影方法将外轮廓展开,检测每个角度对应的爆珠外轮廓上异常突起部分,并计算高度值;最后,综合10个不同角度爆珠的轮廓信息,对爆珠的外表面是否有拖尾缺陷进行判定.分别挑选出200颗拖尾爆珠和200颗合格爆珠样品进行测试,结果表明本文方法的拖尾缺陷识别率≥95%,误检率<1%,最小拖尾识别高度为0.05 mm;选取10批次各1万颗左右的样品进行爆珠放行通过检验,结果显示本文方法与人工灯检方法的偏差分布为[-0.08%,0.21%],能够满足爆珠抽样检验要求.该方法可为卷烟爆珠生产质量控制提供技术支持.
为了考察环境条件对爆珠力学性能的影响,通过测试不同环境条件下爆珠的质量、压破强度、压破形变率和弹性指数,提出了爆珠样品的适宜环境条件.结果表明:①爆珠和爆珠滤棒在"温度(22±1)℃、相对湿度(60±2)%"的环境下调节48 h能够达到温湿度平衡.②爆珠的压破强度、压破形变率和弹性指数在40%~60%相对湿度范围和10~40℃温度范围内略有差异,但差异的程度与样品差异有较大关系.极限温度条件(低于10℃,高于40℃)对爆珠的力学性能有较大的影响,低温冷冻后爆珠的力学性能不可恢复.③爆珠的力学性能在爆珠生产、爆珠滤棒加工和爆珠卷烟加工各环节的温湿度条件下均没有较大差异.