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Simvastatin loaded marine collagen-silk fibroin electrospun nanofiber as a bioactive guided tissue membrane for regenerative and anti-inflammatory therapy 载辛伐他汀海洋胶原-丝素蛋白电纺丝纳米纤维作为生物活性引导组织膜用于再生和抗炎治疗
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-25 DOI: 10.1016/j.jddst.2026.108062
Salma N. Hassan , Mohamed A. Abdelkhalek , Ahmed Y. Gamal , Maged A. El-Kemary , Sara A. Abdel Gaber
Collagen membranes used for Guided Tissue Regeneration (GTR) and wound healing provide adequate biocompatibility, but lack sufficient porosity and can't provide controlled drug delivery needed to support predictable healing. This study aims to address these limitations by developing an electrospun nanofibrous membrane composed of silk fibroin (SF) blended with marine collagen (MCOL) and loaded with Simvastatin (Simva) generating for the first time this bioactive dressing. The membrane was characterized for its morphology, mechanical properties, degradation behavior, and Simva release profile was monitored. Its biological performance was evaluated at the in vitro level and at the in vivo level using full-thickness wound model. The Simva@SF/MCOL membrane showed uniform randomly oriented nanofibers with a mean diameter between 250 and 300 nm and a surface pore diameter of 0.6–1.6 μm. More than 80 % weight loss was achieved over 6 weeks as concluded by assays using artificial saliva. The tensile strength of our Simva/SF/MCOL membrane was 1.7 MPa. Simva release followed Korsmeyer-Peppas model. The membrane was inert to fibroblasts and decreased iNOS and NO level of cells in the scratch wound assay. Animal studies proved the outperformance of Simva @SF/MCOL over commercial collagen membrane and Simva free nanofibers. The wound closure was significantly fostered by the inclusion of Simva as indicated by a closure percentage exceed 90 % within 14 days compared to 80 % in the case of commercial collagen and Simva free nanofibers. That was accompanied with collagen deposition, significant suppression of the inflammatory markers IL-1β and TNF-α. These findings suggest that our first time to be fabricated Simva@SF/MCOL nanofiber offers a bioactive nanotechnology-based membrane outperforming the commercially available membranes used in GTR applications and thus can improve the therapeutic outcome.
用于引导组织再生(GTR)和伤口愈合的胶原膜具有足够的生物相容性,但缺乏足够的孔隙,无法提供支持可预测愈合所需的受控药物输送。本研究旨在通过开发一种由丝素蛋白(SF)与海洋胶原蛋白(MCOL)混合并负载辛伐他汀(Simva)组成的电纺丝纳米纤维膜来解决这些局限性,首次产生这种生物活性敷料。表征了膜的形态、力学性能、降解行为,并监测了Simva释放谱。采用全层创面模型对其体外和体内生物学性能进行了评价。Simva@SF/MCOL膜具有均匀随机取向的纳米纤维,平均直径为250 ~ 300 nm,表面孔径为0.6 ~ 1.6 μm。通过人工唾液测定,在6周内体重减轻了80% %以上。我们的Simva/SF/MCOL膜的拉伸强度为1.7 MPa。Simva的发布遵循了Korsmeyer-Peppas模型。在抓伤实验中,该膜对成纤维细胞具有惰性,并降低了细胞的iNOS和NO水平。动物实验证明Simva @SF/MCOL优于商业胶原膜和不含Simva的纳米纤维。含有Simva的纳米纤维显著促进了伤口愈合,在14天内愈合率超过90% %,而商业胶原蛋白和不含Simva的纳米纤维的愈合率为80% %。同时伴有胶原沉积,炎症标志物IL-1β和TNF-α明显抑制。这些发现表明,我们首次制造的Simva@SF/MCOL纳米纤维提供了一种基于生物活性纳米技术的膜,优于市面上用于GTR应用的膜,从而可以改善治疗效果。
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引用次数: 0
Sustained-release sodium alginate-based metformin/bentonite nanocomposite hydrogel for enhanced wound healing 缓释海藻酸钠基二甲双胍/膨润土纳米复合水凝胶促进伤口愈合
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI: 10.1016/j.jddst.2026.108035
Zahra Rezanejad Gatabi , Mehri Mirhoseini , Mozhgan Abasi , Mohammad Shokati Sayyad , Pedram Ebrahimnejad
Hydrogels are promising wound dressings, yet traditional hydrogels often lack optimal mechanical strength and antimicrobial activity. We developed a novel sodium alginate-based metformin-loaded bentonite (Met-Ben) nanocomposite hydrogel to enhance wound healing. Metformin was encapsulated within bentonite nanoparticles via ion-exchange, achieving an entrapment efficiency of 75.6 % and a drug-loading value of 27.7 %. The nanoparticles had an average size of 364.5 nm and a zeta potential of −8.6 mV. The hydrogel exhibited an increased swelling ratio over 4 h and showed approximately 65 % degradation over 14 days. Sustained metformin release followed Korsmeyer-Peppas kinetics (n = 0.3541, indicating Fickian diffusion). ATR-FTIR and DSC confirmed the chemical integrity and amorphous state of encapsulated metformin. In vitro cytotoxicity assays confirmed its biocompatibility. In vivo, the Met-Ben hydrogel significantly accelerated wound closure (85 % at day 14), increased collagen deposition (p < 0.05, histological scoring), and enhanced fibroblast maturation, re-epithelialization, and neovascularization compared with the control. Gene expression analysis showed downregulation of TNF-α and IL-1β and upregulation of TGF-β (p < 0.01), supporting modulation of inflammation and promotion of tissue regeneration. This study introduces the first sodium alginate–bentonite–metformin nanocomposite hydrogel, offering a dual-action bioactive and structural platform for full-thickness wound healing.
水凝胶是一种很有前途的伤口敷料,但传统的水凝胶往往缺乏最佳的机械强度和抗菌活性。我们开发了一种新型的海藻酸钠基二甲双胍负载膨润土(Met-Ben)纳米复合水凝胶,以促进伤口愈合。通过离子交换将二甲双胍包埋在膨润土纳米颗粒中,包埋效率为75.6%,载药量为27.7%。纳米粒子的平均尺寸为364.5 nm, zeta电位为−8.6 mV。水凝胶在4小时内溶胀率增加,在14天内降解率约为65%。二甲双胍持续释放符合Korsmeyer-Peppas动力学(n = 0.3541,表明菲克扩散)。ATR-FTIR和DSC证实了包封二甲双胍的化学完整性和无定形状态。体外细胞毒性试验证实了其生物相容性。在体内,与对照组相比,Met-Ben水凝胶显著加速伤口愈合(第14天85%),增加胶原沉积(p < 0.05,组织学评分),促进成纤维细胞成熟、再上皮化和新生血管形成。基因表达分析显示TNF-α和IL-1β下调,TGF-β上调(p < 0.01),支持炎症调节和促进组织再生。本研究首次介绍了海藻酸钠-膨润土-二甲双胍纳米复合水凝胶,为全层伤口愈合提供了双重作用的生物活性和结构平台。
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引用次数: 0
Development and evaluation of a graphene oxide–silver nanoparticle– bisdemethoxycurcumin nanocomposite for advanced wound management 氧化石墨烯-银纳米粒子-双去甲氧基姜黄素纳米复合材料的开发与评价
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.jddst.2026.108001
Abdeslam Assafi , Lamia Hejji , Mohamed Amine Zarouki , Youssef Aoulad El Hadj Ali , Luis Pérez-Villarejo , Béla Fiser , Badredine Souhail , Abdelmonaim Azzouz
Wound management remains a significant challenge in clinical practice, requiring effective and innovative solutions. To address this need, this study explores the potential of a novel nanocomposite composed of graphene oxide (GO), silver nanoparticles (AgNPs), and bisdemethoxycurcumin (Cur), denoted as GO@AgNPs@Cur nanocomposite. The successful synthesis of this nanocomposite was confirmed through comprehensive characterization techniques, including Fourier-transform infrared spectroscopy (FTIR), Ultraviolet–Visible Spectroscopy (UV–vis), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and ζ-potential analysis. The therapeutic potential of GO@AgNPs@Cur nanocomposite was evaluated through both in-vivo and in-vitro experiments. In the in-vivo study, full-thickness wounds were carefully induced on the dorsum of mice and treated with GO@AgNPs@Cur nanocomposite. Notably, the composite achieved exceptional wound contraction (97.74 ± 1.10 %) by day 9, significantly outperforming the untreated (53.72 ± 2.11 %) and povidone iodine-treated (58.00 ± 2.64 %) groups. In vitro experiments demonstrated strong antibacterial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) strains, with an MIC and MBC of 117 μg/mL. Additionally, the nanocomposite exhibited excellent antioxidant properties, with a maximum scavenging activity of 85.57 ± 3.96 % and an IC50 of 94.28 μg/mL, as determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. These findings underscore the potential of the GO@AgNPs@Cur nanocomposite as an effective wound healing material with strong antibacterial and antioxidant properties, offering significant promise for advanced wound management.
伤口管理在临床实践中仍然是一个重大挑战,需要有效和创新的解决方案。为了满足这一需求,本研究探索了一种由氧化石墨烯(GO)、银纳米粒子(AgNPs)和双去甲氧基姜黄素(Cur)组成的新型纳米复合材料的潜力,标记为GO@AgNPs@Cur纳米复合材料。通过傅里叶变换红外光谱(FTIR)、紫外可见光谱(UV-vis)、x射线衍射(XRD)、扫描电子显微镜(SEM)和ζ电位分析等综合表征技术,证实了该纳米复合材料的成功合成。通过体内和体外实验评估GO@AgNPs@Cur纳米复合材料的治疗潜力。在体内研究中,在小鼠背部精心诱导全层伤口,并用GO@AgNPs@Cur纳米复合材料处理。值得注意的是,复合材料在第9天达到了异常的创面收缩(97.74±1.10%),明显优于未治疗组(53.72±2.11%)和聚维酮碘治疗组(58.00±2.64%)。体外实验表明,该菌对革兰氏阳性(金黄色葡萄球菌)和革兰氏阴性(大肠杆菌)均有较强的抑菌活性,MIC和MBC均为117 μg/mL。此外,该纳米复合材料表现出优异的抗氧化性能,通过DPPH测定,其最大清除率为85.57±3.96%,IC50为94.28 μg/mL。这些发现强调了GO@AgNPs@Cur纳米复合材料作为一种具有强大抗菌和抗氧化性能的有效伤口愈合材料的潜力,为高级伤口管理提供了重要的希望。
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引用次数: 0
Preclinical development and evaluation of Uricase mRNA-loaded lipid nanoparticles for the treatment of hyperuricemia 载尿酸酶mrna脂质纳米颗粒治疗高尿酸血症的临床前开发和评估
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-20 DOI: 10.1016/j.jddst.2026.108029
Jing Zhang , Jing Wen , Tie Li , Junshuang Xu , Jinbiao Ma , Min Hong , Wei Li
Hyperuricemia (HU), a common metabolic disorder, is characterized by elevated serum uric acid (sUA) levels. Uricase, an enzyme that degrades uric acid(UA) into allantoin, is absent in humans due to a nonsense mutation. Messenger RNA (mRNA)-based protein replacement therapy, known for its efficiency and transient expression, has garnered significant research attention. This study focuses on developing a mRNA therapy for HU using human ancestral uricase ANC19, delivered via lipid nanoparticles (LNPs). We prepared ANC19-LNPs, characterized their physicochemical properties, and evaluated their expression and function in Huh7 cells. Results indicate successful preparation and characterization of ANC19-mRNA, which localizes to peroxisomes and demonstrates UA degradation capability in vitro. Biodistribution was validated in Balb/c mice. Concurrently, a HU mouse model was successfully established using siRNA-mediated knockdown of Uricase-mRNA. In HU mouse models, ANC19-LNPs achieved a 75.63 % UA degradation rate. To validate these promising findings in a more clinically relevant species, the therapy was evaluated in cynomolgus monkeys, where it also showed a therapeutic effect, the area under the curve (AUC) of the concentration-time curve for ANC19-LNPs was 32.647 h∗μg/mL compared to 67.074 h∗μg/mL for the negative control. Biochemical blood tests in cynomolgus monkeys confirmed the safety of ANC19-LNPs. In conclusion, we have successfully developed an effective mRNA-based protein replacement therapy for UA degradation, showing promising efficacy and safety in both in vitro and in vivo studies.
高尿酸血症(HU)是一种常见的代谢性疾病,其特征是血清尿酸(sUA)水平升高。尿酸酶是一种将尿酸(UA)降解为尿囊素的酶,由于无义突变而在人类中缺失。基于信使RNA (mRNA)的蛋白质替代疗法以其高效和瞬时表达而闻名,已经引起了人们的广泛关注。本研究的重点是利用人类祖先的尿酸酶ANC19,通过脂质纳米颗粒(LNPs)递送mRNA治疗HU。我们制备了ANC19-LNPs,表征了它们的理化性质,并评价了它们在Huh7细胞中的表达和功能。结果表明,成功制备并表征了ANC19-mRNA,该mrna定位于过氧化物酶体,并显示出体外UA降解能力。Balb/c小鼠体内生物分布验证。同时,通过sirna介导的敲低Uricase-mRNA,成功建立了HU小鼠模型。在HU小鼠模型中,ANC19-LNPs的UA降解率达到75.63%。为了在更多临床相关物种中验证这些有希望的发现,对食蟹猴进行了治疗评估,在那里它也显示出治疗效果,ANC19-LNPs的浓度-时间曲线下面积(AUC)为32.647 h∗μg/mL,而阴性对照为67.074 h∗μg/mL。食蟹猴血液生化检测证实了ANC19-LNPs的安全性。总之,我们已经成功开发了一种有效的基于mrna的蛋白替代疗法,用于UA降解,在体外和体内研究中都显示出良好的疗效和安全性。
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引用次数: 0
Genistein-loaded mesenchymal stem cells (MSCs)-derived exosomes: A novel drug carrier for targeted osteosarcoma treatment via PPARγ pathway 负载染料木素的间充质干细胞(MSCs)衍生外泌体:通过PPARγ途径靶向骨肉瘤治疗的新型药物载体
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-14 DOI: 10.1016/j.jddst.2025.107862
Zhiqian Gu , Songou Zhang , Guoqing Li , Xudong Hu , Nanjian Xu , Yang Wang , Jian Ruan , Weihu Ma , Hong Chen
Osteosarcoma, a very aggressive bone cancer, poses considerable therapeutic hurdles because it is resistant to conventional therapies. The objective of this work was to develop a novel genistein-based therapeutic formulation by encapsulating the compound into exosomes derived from mesenchymal stem cells (MSCs) and to evaluate its in vitro efficacy against osteosarcoma. The physicochemical characteristics of the genistein-loaded exosomes (Exo-Gen) were analysed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) Osteosarcoma cell line MG63 were treated with Exo-Gen, and their effects on cell viability, cellular uptake and migration were evaluated using in vitro CCK-8 assay, flow cytometry and Transwell assay. The Western blot assay was used to evaluate the protein expression of the PPARγ pathway proteins (PPARγ, PTEN, P21, Cyclin B1, Bcl-2 and Survivin). RT-qPCR has been employed to determine the mRNA expression levels of PPARγ and PTEN. Compared to the free genistein (Free-Gen), the produced Exo-Gen demonstrated improved cellular uptake efficiency and cytotoxicity in the MG63 cell line, with half-maximal inhibitory concentrations (IC50) of 10.18 μg/mL for Free-Gen and 6.54 μg/mL for Exo-Gen. Exo-Gen substantially boosted PPARγ expression in osteosarcoma cells, relative to Free-Gen. Genistein is a non-toxic PPARγ activator which effectively inhibits the osteosarcoma cell growth when administered through exosomes. In addition, in vivo studies utilizing a tumour-bearing mice model corroborated the enhanced anticancer efficacy and biocompatibility of Exo-Gen. This approach significantly improves the distribution and effectiveness of genistein, rendering it as an ideal platform for future cancer therapy.
骨肉瘤是一种侵袭性很强的骨癌,由于对传统疗法具有耐药性,因此在治疗上存在相当大的障碍。本研究的目的是通过将染料木素包埋在间充质干细胞(MSCs)的外泌体中,开发一种新的基于染料木素的治疗制剂,并评估其体外治疗骨肉瘤的疗效。采用透射电镜(TEM)和纳米颗粒跟踪分析(NTA)分析了负载染料木素的外泌体(Exo-Gen)的理化特性,并利用体外CCK-8、流式细胞术和Transwell实验评估了Exo-Gen对MG63骨肉瘤细胞活力、细胞摄取和迁移的影响。Western blot检测PPARγ通路蛋白(PPARγ、PTEN、P21、Cyclin B1、Bcl-2和Survivin)的表达情况。RT-qPCR检测PPARγ和PTEN mRNA表达水平。与游离染料木素(free - gen)相比,生成的Exo-Gen在MG63细胞系中具有更高的细胞摄取效率和细胞毒性,其半最大抑制浓度(IC50)为10.18 μg/mL, Exo-Gen为6.54 μg/mL。与Free-Gen相比,Exo-Gen显著提高了骨肉瘤细胞中PPARγ的表达。染料木素是一种无毒的PPARγ激活剂,通过外泌体给药可有效抑制骨肉瘤细胞的生长。此外,利用荷瘤小鼠模型进行的体内研究证实了Exo-Gen增强的抗癌功效和生物相容性。这种方法显著改善了染料木素的分布和有效性,使其成为未来癌症治疗的理想平台。
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引用次数: 0
Erythritol-based co-amorphous systems for Indomethacin: Enhancing solubility, bioavailability, and therapeutic efficacy 吲哚美辛的赤藓糖醇共无定形体系:提高溶解度、生物利用度和治疗效果
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-08 DOI: 10.1016/j.jddst.2026.107987
Abhijeet A. Aher, Karimunnisa S. Shaikh
This study explores the use of erythritol (ERY) and other co-formers, including xylitol (XYL) and biotin (BIO), in developing co-amorphous formulations (CAM) to improve the solubility, dissolution, and stability of poorly water-soluble drugs. Molecular docking revealed strong interactions between ERY and Indomethacin (IMC), supporting its role as a stabilizing co-former. Solubility parameter analysis confirmed excellent compatibility between IMC and ERY, ensuring homogeneity and preventing phase separation. The optimized IMC-ERY formulation, prepared by spray drying, achieved 99.03 % drug release within 120 min with a glass transition temperature (Tg) of 119.2 °C. Pharmacokinetic studies showed a 3.73-fold increase in bioavailability for the IMC-ERY CAM compared to crystalline IMC. Pharmacodynamic evaluation demonstrated sustained anti-inflammatory effects, with 74.25 % inhibition of paw edema at 12 h, showcasing superior performance compared to the control group and pure IMC. Histopathological analysis confirmed minimal liver and kidney toxicity, indicating the safety of the formulation. This research establishes ERY as an effective stabilizing co-former, maintaining IMC in an amorphous state, enhancing solubility, and improving therapeutic efficacy.
本研究探讨了赤藓糖醇(ERY)和其他共成型物,包括木糖醇(XYL)和生物素(BIO),在开发共无定形制剂(CAM)中的应用,以提高水溶性差药物的溶解度、溶出度和稳定性。分子对接揭示了ERY与吲哚美辛(IMC)之间的强相互作用,支持其作为稳定共原体的作用。溶解度参数分析证实了IMC和ERY具有良好的相容性,保证了均匀性,防止了相分离。通过喷雾干燥法制备的最佳IMC-ERY制剂在120 min内释药99.03%,玻璃化转变温度(Tg)为119.2℃。药代动力学研究表明,与结晶IMC相比,IMC- ery CAM的生物利用度提高了3.73倍。药效学评估显示持续的抗炎作用,12 h时对足跖水肿的抑制率为74.25%,与对照组和纯IMC相比,表现出优越的性能。组织病理学分析证实了最小的肝和肾毒性,表明该制剂的安全性。本研究确定了ERY作为一种有效的稳定共原体,可以维持IMC处于无定形状态,增强溶解度,提高治疗效果。
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引用次数: 0
Preparation of polyethylene glycol-polycaprolactone-polyethyleneimine amphiphilic block copolymer magnetic nanocarriers for targeting treatment of hepatocellular carcinoma 聚乙二醇-聚己内酯-聚乙烯亚胺两亲性嵌段共聚物磁性纳米载体靶向治疗肝癌的制备
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-07 DOI: 10.1016/j.jddst.2026.107995
Hao Wang , Minyi Zhang , Lijun You, Shaoyun Wang
The development of multifunctional nanocarrier systems capable of achieving high drug loading, prolonged controlled release, and integrated diagnostic functions for the precise treatment of hepatocellular carcinoma represents a pressing clinical demand. This study aims to design a multifunctional nanocarrier system that combines sustained drug release, diagnostic imaging capabilities, and active tumor-targeting properties to enable synergistic therapeutic effects. A novel magnetic amphiphilic triblock copolymer (PEG-PCL-PEI) micellar nanocarrier was developed, incorporating dual-targeting mechanisms: magnetic targeting via Fe3O4 nanoparticles and molecular targeting via folic acid conjugation. The system was loaded with doxorubicin (Dox) and small interfering RNA (siRNA) to achieve precise targeting of hepatic tumors. The average particle size, drug loading efficiency (LE), and encapsulation efficiency (EE) of the micelles were measured at 225 nm, 2.91 %, and 84.26 %, respectively, with a Dox release rate reaching 80 % after 35 h. The T2 relaxation rate of the formulation was determined to be 12.21 mM−1 s−1, demonstrating excellent MRI contrast performance. Comprehensive evaluations of the drug delivery efficiency and in vitro biological activities revealed that the drug-loaded micelles inhibited the migration of human hepatocellular carcinoma HepG2 cells by 62.68 % within 24 h, indicating a strong anti-migratory effect. Furthermore, Dox induced reactive oxygen species (ROS) generation in cancer cells, while the released siRNA downregulated Bcl-2 expression, thereby synergistically promoting apoptosis in hepatocellular carcinoma cells. In vivo imaging and tumor inhibition studies in animal models demonstrated that the micelles significantly suppressed tumor growth without inducing notable toxicity to other organs. These findings collectively suggest that the developed micellar nanocarrier system holds substantial promise for the effective treatment of liver tumors.
开发多功能纳米载体系统,以实现高药物负荷、长时间控释和综合诊断功能,以精确治疗肝细胞癌,是迫切的临床需求。本研究旨在设计一种多功能纳米载体系统,该系统结合了药物持续释放、诊断成像能力和活性肿瘤靶向特性,以实现协同治疗效果。研制了一种新型磁性两亲性三嵌段共聚物(PEG-PCL-PEI)胶束纳米载体,该载体具有双靶向机制:通过Fe3O4纳米颗粒进行磁性靶向和通过叶酸偶联进行分子靶向。该系统负载多柔比星(Dox)和小干扰RNA (siRNA),实现肝脏肿瘤的精确靶向。在225 nm处测定了胶束的平均粒径、载药效率(LE)和包封效率(EE),分别为2.91%和84.26%,35 h后Dox释放率达到80%,T2松弛率为12.21 mM−1 s−1,具有良好的MRI造影剂性能。综合评价药物传递效率和体外生物活性发现,载药胶束在24 h内对人肝癌HepG2细胞的迁移抑制率为62.68%,具有较强的抗迁移作用。此外,Dox诱导癌细胞产生活性氧(ROS),同时释放的siRNA下调Bcl-2的表达,从而协同促进肝癌细胞凋亡。动物模型的体内成像和肿瘤抑制研究表明,胶束可以显著抑制肿瘤生长,而不会对其他器官产生明显的毒性。这些发现共同表明,已开发的胶束纳米载体系统对有效治疗肝脏肿瘤具有实质性的希望。
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引用次数: 0
CRISPR-based antimicrobials and nanomotor technologies for drug-resistant biofilms 基于crispr的抗菌剂和耐药生物膜的纳米运动技术
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.jddst.2026.108002
Qianqian Sun , Vincent Kawuribi , Yiyang Xie , Haiqing Xu , Shaohui Zheng
Antimicrobial resistance (AMR), particularly within biofilm-associated infections, has emerged as a critical global health challenge, rendering many conventional antibiotics ineffective. Two promising and rapidly evolving strategies, CRISPR-based antimicrobials and micro/nanomotor (MNM) systems, have independently shown potential in addressing this crisis. CRISPR-Cas platforms provide unmatched genetic precision, enabling selective bacterial killing or re-sensitization through the targeting of essential or resistance genes (e.g., mecA, blaNDM-1). Separately, MNMs demonstrate active penetration of biofilms, localized delivery of antimicrobials, and mechanical or chemical disruption of biofilm matrices, with propulsion mechanisms ranging from chemical fuels to magnetic and acoustic guidance. In this review, we comprehensively examine the current state of knowledge on CRISPR-based antimicrobials and nanomotor-mediated antibacterial strategies, highlighting their mechanisms, experimental advances, and limitations. We then present a perspective on their potential convergence into CRISPR-driven nanomotor systems, an emerging frontier not yet realized experimentally but conceptually poised to overcome longstanding delivery challenges. We discuss possible design frameworks, delivery strategies, and translational hurdles, while comparing this hybrid approach with existing antimicrobial delivery platforms such as bacteriophages and nanoparticles. By combining the genetic precision of CRISPR with the active penetration and controllability of nanomotors, such integrated systems may represent a next-generation paradigm for the targeted disruption of multidrug-resistant (MDR) biofilms. This article thus serves both as a comprehensive review of the current literature and a forward-looking perspective on future directions in precision antimicrobial therapy.
抗菌素耐药性(AMR),特别是在生物膜相关感染中,已成为一项重大的全球卫生挑战,使许多传统抗生素无效。基于crispr的抗菌剂和微/纳米马达(MNM)系统这两种有前景且发展迅速的策略分别显示出解决这一危机的潜力。CRISPR-Cas平台提供了无与伦比的遗传精度,能够通过靶向必需或抗性基因(例如,mecA, blaNDM-1)选择性杀死细菌或重新致敏。另外,纳米颗粒还表现出生物膜的主动渗透、抗菌剂的局部递送以及生物膜基质的机械或化学破坏,其推进机制包括从化学燃料到磁和声制导。在这篇综述中,我们全面研究了基于crispr的抗菌剂和纳米马达介导的抗菌策略的现状,重点介绍了它们的机制、实验进展和局限性。然后,我们提出了它们与crispr驱动的纳米运动系统的潜在融合的观点,这是一个尚未在实验上实现的新兴前沿,但在概念上准备克服长期存在的交付挑战。我们讨论了可能的设计框架、传递策略和转化障碍,同时将这种混合方法与现有的抗菌素传递平台(如噬菌体和纳米颗粒)进行了比较。通过将CRISPR的遗传精度与纳米马达的主动渗透和可控性相结合,这种集成系统可能代表了靶向破坏多药耐药(MDR)生物膜的下一代范例。因此,本文既是对当前文献的全面回顾,也是对未来精准抗菌治疗方向的前瞻性展望。
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引用次数: 0
Gunnera perpensa L. - mediated gold nanoparticles with enhanced anti-gonococcal activity 甘草介导的金纳米颗粒抗淋球菌活性增强
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-07 DOI: 10.1016/j.jddst.2026.107977
Tanyaradzwa Tiandra Dembetembe , Danielle Twilley , Jacqueline Maphutha , Marco Nuno De Canha , Velaphi Clement Thipe , Vusani Mandiwana , Michel Lonji Kalombo , Rirhandzu Rikhotso , Suprakas Sinha Ray , Namrita Lall , Quenton Kritzinger
Gonorrhoea is the second most prevalent sexually transmitted disease (STD) worldwide, with its treatment increasingly compromised by antibiotic resistance to available treatments. This has led to the investigation of bioactive plants as sources for novel drug development, with plant-based nanoparticles showing promise in treating STDs. This study aimed to evaluate the anti-gonococcal activity and cytotoxicity of the ethanolic root extract of Gunnera perpensa L. (GP) and to determine whether synthesis of gold nanoparticles (AuNPs) from GP showed enhanced biological activity. Characterization of the nanoparticles was performed using ultraviolet–visible spectrometry (UV–Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Lastly, the anti-gonococcal activity and cytotoxicity of GP and GP-AuNPs were evaluated. The AuNPs exhibited a surface plasmon resonance at 536 nm, confirming the successful synthesis of nanoparticles, with a hydrodynamic size of 127.20 nm and a core size of 39.51 nm. The GP-AuNPs showed enhanced anti-gonococcal activity compared to GP with a minimum inhibitory concentration (MIC) of 10.40 and 46.70 μg/mL, respectively. Cytotoxicity was evaluated on human keratinocytes (HaCaT), human monocytes (THP-1), and STD-related human cervical adenocarcinoma (HeLa), with GP-AuNPs exhibiting fifty percent inhibitory concentrations (IC50) of 22.12 ± 0.52, 27.53 ± 6.02, and >38.96 μg/mL, respectively. In contrast, GP showed IC50 values > 400 μg/mL against all tested cell lines. These findings indicate that GP-AuNPs exhibit significant anti-gonococcal activity with greater selectivity for Neisseria gonorrhoeae over non-cancerous (HaCaT and THP-1) cells, as evidenced by selectivity indices (SIs) > 2. These findings suggest that both GP and GP-AuNP possess potential as lead candidates for the treatment of gonorrhoea. Their limited antiproliferative activity against HeLa cells (SI < 0.7) indicates they are unsuitable for treating STD-associated cervical cancers. To the best of our knowledge, no published studies have investigated the effect of plant-synthesized nanoparticles on their activity against N. gonorrhoeae; therefore, this is the first use of GP-AuNPs against N. gonorrhoeae, advancing plant-based nanomedicine for STDs.
淋病是世界上第二大流行的性传播疾病(STD),由于抗生素对现有治疗方法产生耐药性,淋病的治疗日益受到影响。这导致了对生物活性植物作为新药开发来源的研究,基于植物的纳米颗粒在治疗性传播疾病方面显示出希望。本研究旨在评价甘菊(Gunnera perpensa L., GP)乙醇根提取物(Gunnera perpensa L., GP)的抗淋球菌活性和细胞毒性,并确定由GP合成的金纳米颗粒(AuNPs)是否具有增强的生物活性。采用紫外可见光谱(UV-Vis)、透射电子显微镜(TEM)、动态光散射(DLS)、Zeta电位、傅里叶变换红外光谱(FTIR)和x射线衍射(XRD)对纳米颗粒进行了表征。最后,对GP和GP- aunps的抗淋球菌活性和细胞毒性进行了评价。AuNPs在536 nm处表现出表面等离子体共振,证实了纳米颗粒的成功合成,其水动力尺寸为127.20 nm,核尺寸为39.51 nm。与GP相比,GP- aunps的抗淋球菌活性增强,最低抑制浓度(MIC)分别为10.40和46.70 μg/mL。对人角化细胞(HaCaT)、人单核细胞(THP-1)和性传播疾病相关人宫颈腺癌(HeLa)的细胞毒性进行了评价,结果表明,gps - aunps的50%抑制浓度(IC50)分别为22.12±0.52、27.53±6.02和38.96 μg/mL。而GP对所有细胞株的IC50值均为400 μg/mL。这些发现表明GP-AuNPs具有显著的抗淋球菌活性,对非癌性(HaCaT和THP-1)淋球菌具有更高的选择性,选择性指数(SIs)证明了这一点[gt; 2]。这些发现表明GP和GP- aunp都具有作为淋病治疗的主要候选药物的潜力。它们对HeLa细胞有限的抗增殖活性(SI < 0.7)表明它们不适合治疗性传播疾病相关的宫颈癌。据我们所知,没有发表的研究调查了植物合成纳米颗粒对淋病奈瑟菌活性的影响;因此,这是首次使用GP-AuNPs治疗淋病奈瑟菌,推进了基于植物的性传播疾病纳米药物。
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引用次数: 0
CD44-targeted and pH-degradable hollow mesoporous silica nanocarriers for cancer therapy cd44靶向和ph可降解中空介孔二氧化硅纳米载体用于癌症治疗
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-03-01 Epub Date: 2026-01-21 DOI: 10.1016/j.jddst.2026.108045
Yi-Ching Tsai , Natesan Thirumalaivasan , Shu-Pao Wu
Targeted drug delivery systems are crucial for cancer treatment, as they boost therapeutic effectiveness while minimizing systemic toxicity. In this study, we developed pH-degradable hollow mesoporous silica nanoparticles (HMON) functionalized with hyaluronic acid (HA) for CD44-targeted drug delivery. Aryl imine organosilane was utilized to confer pH-responsiveness to the HMON, enabling controlled drug release in the mildly acidic tumor microenvironment. In vitro studies have shown that DOX@HMON-HA significantly enhances DOX uptake in CD44-overexpressing tumor cells, such as HeLa and HCT-116, leading to substantial cytotoxic effects. In contrast, CD44-low expressing cells like MCF-7 exhibit minimal DOX uptake and reduced cytotoxicity. In vivo studies further validated the therapeutic efficacy of DOX@HMON-HA, showing effective tumor growth suppression without observable systemic toxicity. These findings underscore the potential of pH-degradable hyaluronan (HA)-modified silica nanoparticles as an effective strategy for targeted cancer therapy.
靶向给药系统对癌症治疗至关重要,因为它们可以提高治疗效果,同时最大限度地减少全身毒性。在这项研究中,我们开发了ph可降解的中空介孔二氧化硅纳米颗粒(HMON),透明质酸(HA)功能化,用于cd44靶向药物递送。芳基亚胺有机硅烷被用来赋予HMON的ph响应性,从而在轻度酸性肿瘤微环境中控制药物释放。体外研究表明,DOX@HMON-HA可显著增强过表达cd44的肿瘤细胞(如HeLa和HCT-116)对DOX的摄取,从而产生显著的细胞毒性作用。相比之下,cd44低表达的细胞如MCF-7表现出最小的DOX摄取和降低的细胞毒性。体内研究进一步验证了DOX@HMON-HA的治疗效果,显示出有效的肿瘤生长抑制,没有明显的全身毒性。这些发现强调了ph可降解透明质酸修饰二氧化硅纳米颗粒作为靶向癌症治疗的有效策略的潜力。
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引用次数: 0
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Journal of Drug Delivery Science and Technology
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