Advanced Healthcare Materials
·
2024
·
IF 10
Mingxing Li,Xuwei Shang,Haiya Lou,Zixu Wang,Shanshan Xiang,Yihe Qiu,Fuqiang Hu,Fangying Yu,Hong Yuan
Recently, nanotechnology-based drug delivery platforms in treating pulmonary arterial hypertension (PAH) have gradually emerged. However, large mechanical stress and shear stress in blood vessels greatly affect the retention of nanopreparative materials at lesion sites, severely limiting nanotechnology-based drug delivery. Herein, a stimuli-responsive nanocraft is rationally designed by actively anchoring E-selectin overexpressed on pulmonary arterial endothelial cells (PAECs), under hypoxic conditions, allowing effective accumulation and retention of the drug at the lesion site. Briefly, a nitrobenzene group is incorporated into the framework of a nanocarrier, and then it is simultaneously linked with chitosan. Additionally, the surface of the nanocarrier with sialic acid (SA) and encapsulated the clinically used drug ambrisentan (Am), which enables the anchoring of E-selectin and subsequent drug delivery is modifed. This system facilitates intercellular transport to pulmonary artery smooth muscle cells (PASMCs) when targeting PAECs and specifically responds to a reductive hypoxic microenvironment with elevated nitroreductase in PASMCs. Moreover, compared with free Am, nanoencapsulation and SA-PEG 2000 -NH 2 prolong the blood circulation time, achieving better therapeutic outcomes in preventing vascular remodeling and reversing systolic dysfunction. The originality and contribution of this work reveal the promising value of this pulmonary arterial anchoring stimuli-responsive nanocraft as a novel therapeutic strategy for satisfactory PAH treatment.
研究领域:
纳米技术
·
药学
·
心血管医学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Yanan Wang,Xutao Ma,Xinyuan Wang,Liru Liu,Xue Zhang,Qiuyue Wang,Yingfei Zhu,Huanhua Xu,Liangmin Yu,Zhiyu He
The scarcity of effective neuroprotective agents and the presence of blood-brain barrier (BBB)-mediated extremely inefficient intracerebral drug delivery are predominant obstacles to the treatment of cerebral ischemic stroke (CIS). Herein, ROS-responsive borneol-based amphiphilic polymeric NPs are constructed by using traditional Chinese medicine borneol as functional blocks that served as surface brain-targeting ligand, inner hydrophobic core for efficient drug loading of membrane-permeable calcium chelator BAPTA-AM, and neuroprotective structural component. In MCAO mice, the nanoformulation (polymer: 3.2 mg·kg −1 , BAPTA-AM: 400 µg·kg −1 ) reversibly opened the BBB and achieved high brain biodistribution up to 12.7%ID/g of the total administered dose after 3 h post single injection, effectively restoring intracellular Ca 2+ and redox homeostasis, improving cerebral histopathology, and inhibiting mitochondrial PI3K/Akt/Bcl-2/Bax/Cyto-C/Caspase-3,9 apoptosis pathway for rescuing dying neurons (reduced apoptosis cell from 59.5% to 7.9%). It also remodeled the inflammatory microenvironment in cerebral ischemic penumbra by inhibiting astrocyte over-activation, reprogramming microglia polarization toward an anti-inflammatory phenotype, and blocking NF-κB/TNF- α /IL-6 signaling pathways. These interventions eventually reduced the cerebral infarction area by 96.3%, significantly improved neurological function, and restored blood flow reperfusion from 66.2% to ≈100%, all while facilitating BBB repair and avoiding brain edema. This provides a potentially effective multiple-stage sequential treatment strategy for clinical CIS.
研究领域:
药学
·
神经科学
·
药物递送系统
·
传统中药
·
中风治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2021
·
IF 4.098
Xiaotao Liu,Shanshan Xing,Yuanteng Xu,Ruiqing Chen,Chang Lin,Liangqia Guo
Graphitic carbon nitride (g-C 3 N 4 ) has been shown as a promising visible-light photosensitizer for photodynamic therapy (PDT) application. Nevertheless, its therapeutic efficiency is limited by the low efficiency of visible-light utilization. To overcome this issue, 3-amino-1,2,4-triazole-derived graphitic carbon nitride nanosheets (g-C 3 N 5 NSs) are prepared for PDT application. The addition of nitrogen-rich triazole group into the g-C 3 N 4 motif significantly makes the light absorption of g-C 3 N 5 NSs red-shift with the band gap down to 1.95 eV, corresponding to a absorption edge at a wavelength of 636 nm. g-C 3 N 5 NSs generate superoxide anion radicals (O 2 •– ) and singlet oxygen ( 1 O 2 ) under the irradiation of a low-intensity white light emitting diode. Owing to the high efficiency of visible-light utilization, g-C 3 N 5 NSs show about 9.5 fold photocatalytic activity of g-C 3 N 4 NSs. In vitro anticancer studies based on the results of CCK-8 assay, Calcein-AM/PI cell-survival assay and photo-induced intracellular ROS level analysis in living HeLa cells demonstrate the potential of g-C 3 N 5 NSs as a low-toxic and biocompatible high-efficient photosensitizer for PDT.
研究领域:
材料科学
·
纳米技术
·
光动力治疗
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Yanan Wang,Deyao Qian,Xinyuan Wang,Xue Zhang,Zerui Li,Xinlei Meng,Liangmin Yu,Xuefeng Yan,Zhiyu He
Developing strategies to target injured pancreatic acinar cells (PACs) in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of acute pancreatitis (AP). We designed and synthesized a trypsin-cleavable organosilica precursor bridged by arginine-based amide bonds, leveraging trypsin’s ability to selectively identify guanidino groups on arginine via Asp189 at the active S1 pocket and cleave the carboxy-terminal (C-terminal) amide bond via catalytic triads. The precursors were incorporated into the framework of mesoporous silica nanoparticles (MSNs) for encapsulating the membrane-permeable Ca2+ chelator BAPTA-AM with a high loading content (∼43.9%). Mesenchymal stem cell membrane coating and surface modification with PAC-targeting ligands endow MSNs with inflammation recruitment and precise PAC-targeting abilities, resulting in the highest distribution at 3 h in the pancreas with 4.7-fold more accumulation than that of naked MSNs. The outcomes transpired as follows: After bioinspired MSNs’ skeleton biodegradation by prematurely and massively activated trypsin, BAPTA-AM was on-demand released in injured PACs, thereby effectively eliminating intracellular calcium overload (reduced Ca2+ level by 81.3%), restoring cellular redox status, blocking inflammatory cascades, and inhibiting cell necrosis by impeding the IκBα/NF-κB/TNF-α/IL-6 and CaMK-II/p-RIP3/p-MLKL/caspase-8,9 signaling pathways. In AP mice, a single dose of the formulation significantly restored pancreatic function (lipase and amylase reduced more by 60%) and improved the survival rate from 50 to 91.6%. The formulation offers a potentially effective strategy for clinical translation in AP treatment.
研究领域:
纳米医学
·
药学
·
生物医学工程
·
分子生物学
·
炎症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SOILS AND SEDIMENTS
·
2016
·Vol. 17
·期 3
·841-851
·
IF 2.206
Cao Jiling,Feng Youzhi,Lin Xiangui,Wang Junhua,Xie Xinqiao
Purpose As a ubiquitous symbiotic fungus, the responses and the feedback of arbuscular mycorrhizal (AM) fungi to engineered nanoparticles (ENPs) remain unknown as well as the underlying mechanisms. The objective of this investigation was to figure out the influence of iron oxide magnetic nanoparticles (Fe 3 O 4 NPs) on AM fungal community, the underlying mechanisms, and the possible consequences of AM fungi-plant involved soil ecosystem. Materials and methods A greenhouse pot experiment was established to investigate the responses of maize ( Zea may L.) growth and AM fungal community to differential application levels (0.1, 1.0, and 10.0 mg kg −1 ) of iron oxide magnetic nanoparticles (Fe 3 O 4 NPs) or microscale magnetic iron oxide (bulk Fe 3 O 4 ). The AM fungal community composition and diversity were analyzed by high-throughput sequencing. The plant biomass, phosphorus (P) acquisitions, Fe concentration in plant shoots, catalase (CAT) activity, root mycorrhizal colonization rate, and glomalin-related soil protein (GRSP) contents were determined. In the meantime, the soil P supply efficiency, soil pH, and dissolved organic carbon contents (DOC) were analyzed as well as soil-soluble Fe content. Results and discussion Fe 3 O 4 NPs at 10.0 mg kg −1 (the high concentration) could be toxic to AM fungi by directly decreasing their diversity significantly ( p < 0.05) and shifting their community structure, compared to the control and bulk Fe 3 O 4 . The similar toxicity was observed for host plant by the significant increases ( p < 0.05) in Fe concentration in plant shoots and CAT activity. Consequently, the biomass of the host plant and the photosynthetic carbon left for AM fungi were obviously decreased ( p < 0.05). The direct and indirect influences of Fe 3 O 4 NPs at high concentration result in the reduction of AM fungal ecological function, such as the significantly decreased ( p < 0.05) root mycorrhizal colonization, soil GRSP content, and alkaline phosphatase activity. This process, in return, could deteriorate the nutrient provision of AM fungi for plant. As evidence, soil available P content and P nutrition in plants were significantly decreased ( p < 0.05). Conclusions The Fe 3 O 4 NPs at high concentration would destroy the mutual interaction of AM fungi-plant and negatively influence the soil carbon accumulation and P cycling, both of which go against crop yield and soil fertility.
研究领域:
环境科学
·
微生物学
·
农学
·
生态学
✓ 已验证
DOI
高影响因子
Advanced Science
·
2023
·Vol. 10
·期 14
·2207448
·
IF 15.1
Jiahui Yan,Jingwen Zhang,Yanan Wang,Hong Liu,Xueping Sun,Aixin Li,Pengfei Cui,Liangmin Yu,Xuefeng Yan,Zhiyu He
Pyroptosis, systemic inflammation, and mitochondrial apoptosis are the three primary contributors to sepsis's multiple organ failure, the ultimate cause of high clinical mortality. Currently, the drugs under development only target a single pathogenesis, which is obviously insufficient. In this study, an acid-responsive hollow mesoporous polydopamine (HMPDA) nanocarrier that is highly capable of carrying both the hydrophilic drug NAD + and the hydrophobic drug BAPTA-AM, with its outer layer being sealed by the inflammatory targeting peptide PEG-LSA, is developed. Once targeted to the region of inflammation, HMPDA begins depolymerization, releasing the drugs NAD + and BAPTA-AM. Depletion of polydopamine on excessive reactive oxygen species production, promotion of ATP production and anti-inflammation by NAD + replenishment, and chelation of BAPTA (generated by BA-AM hydrolysis) on overloaded Ca 2+ can comprehensively block the three stages of sepsis, i.e., precisely inhibit the activation of pyroptosis pathway (NF- κ B-NLRP3-ASC-Casp-1), inflammation pathway (IL-1 β , IL-6, and TNF- α ), and mitochondrial apoptosis pathway (Bcl-2/Bax-Cyt-C-Casp-9-Casp-3), thereby restoring intracellular homeostasis, saving the cells in a state of “critical survival,” further reducing LPS-induced systemic inflammation, finally restoring the organ functions. In conclusion, the synthesis of this agent provides a simple and effective synergistic drug delivery nanosystem, which demonstrates significant therapeutic potential in a model of LPS-induced sepsis.
研究领域:
药理学
·
纳米技术
·
免疫学
·
细胞生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Wang Zhiwei,Sun Lingshun,Wang Weixing,Wang Zheng,Shi Ge,Dai Honglian,Yu Aixi
Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix (ECM) and growth factors and causes severe vascular damage, which seriously hinders diabetic wound healing. To solve these issues, a double-network porous hydrogel composed of poly (methyl methacrylate-co-acrylamide) (p(MMA-co-AM)) and polyvinyl alcohol (PVA) was constructed by the high internal phase emulsions (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit matrix metalloproteinases (MMPs), increase angiogenesis, and improve microcirculation. The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies, high porosity, high specific surface area, excellent mechanical properties, and suitable swelling properties. Meanwhile, the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release. In addition, both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds, increasing growth factor secretion, improving vascularization, increasing collagen deposition, and promoting re-epithelialization. Therefore, this study provided a reliable therapeutic strategy for diabetic wound healing, some theoretical basis, and new insights for the rational design and preparation of wound hydrogel dressings with high porosity, high drug-loading performance, and excellent mechanical properties.
研究领域:
材料科学
·
生物医学工程
·
药剂学
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Haolin Cai,Dongzhi Zhang,Hao Zhang,Mingcong Tang,Zhenyuan Xu,Hui Xia,Kangshuai Li,Jun Wang
Flexible strain sensors and flexible supercapacitors have generated a lot of interest because of their great potential to be used in flexible electronic equipment. Ionic hydrogels are ideal for the preparation of strain sensors and supercapacitor electrolytes, so the design of a multifunctional ionic conductive hydrogel is the key to obtain both high-performance strain sensors and flexible all-solid-state supercapacitors. During our work, trehalose and LiCl were added concurrently to the P(AM-co-AA) polymer network to prepare a multifunctional ionic conductive hydrogel combining ultra stretchability (elongation at break up to 4529%), high ionic conductivity, self-adhesive and freeze-resistant moisturizing properties. The ionic conductive hydrogel was encapsulated into a strain sensor, which has excellent sensing performance, achieving a great detection range (0–4200%) and high sensitivity (GF = 3.59 in the strain range of 2200–4200%). The strain sensor was applied to human motion detection, demonstrating precise detection behavior for joint flexion and muscle movement. The ionic conductive hydrogel was assembled with flexible fabric electrodes loaded with carbon nanotubes (CNTs) and MXene to form a sandwich-type supercapacitor. The supercapacitor exhibited high areal capacitance (148.2 mF/cm 2 ), excellent cycling performance, outstanding stability and good low temperature resistance.
研究领域:
材料科学
·
电化学
·
柔性电子
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2015
·
IF 3.529
Demei Xu,Chuanyang Su,Xiufang Song,Qiong Shi,Juanli Fu,Lihua Hu,Xiaomin Xia,Erqun Song,Yang Song
Organisms are able to respond to environmental insult to maintain cellular homeostasis, which include the activation of a wide range of cellular adaptive responses with tightly controlled mechanisms. The endoplasmic reticulum (ER) is an organelle responsible for protein folding and calcium storage. ER stress leads to the accumulation of unfolded proteins in the ER lumen. To be against or respond to this effect, cells have a comprehensive signaling system, called unfolded protein response (UPR), to restore homeostasis and normal ER function or activate the cell death program. Therefore, it is critical to understand how environmental insult regulates the ingredients of ER stress and UPR signalings. Previously, we have demonstrated that polychlorinated biphenyl (PCB) quinone caused oxidative stress, cytotoxicity, genotoxicity, and apoptosis in HepG2 cells. Here, we investigated the role of a PCB quinone, PCB29-pQ on ER stress, UPR, and calcium release. PCB29-pQ markedly increased the hallmark genes of ER stress, namely, glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein (CHOP) on both protein and mRNA levels in HepG2 cells. We also confirmed PCB29-pQ induced ER morphological defects by using transmission electron microscopy. Moreover, PCB29-pQ induced intracellular calcium accumulation and calpain activity, which were significantly inhibited by the pretreatment of BAPTA-AM (Ca2+ chelator). These results were correlated with the outcome that PCB29-pQ induces ER stress-related apoptosis through caspase family gene 12, while salubrinal and Z-ATAD-FMK (a specific inhibitor of caspase 12) partially ameliorated this effect, respectively. N-Acetyl-l-cysteine (NAC) scavenged ROS formation and consequently alleviated PCB29-pQ-induced expression of ER stress-related genes. In conclusion, our result demonstrated for the first time that PCB quinone leads to ROS-dependent induction of ER stress, and UPR and calcium release in HepG2 cells, and the evaluation of the perturbations of ER stress, UPR, and calcium signaling provide further information on the mechanisms of PCB-induced toxicity.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yang Pang,Zhichuang Qi,Liangliang Cui,Zhangmi Huang,Chunyan Hu,Zhijia Zhu,Baojiang Liu
Photonic crystal hydrogels (PCHs) are innovative materials that translate imperceptible deformations and humidity changes into visible colors, broadening the applications of photonics in bioengineering and smart materials. To overcome poor mechanical properties of traditional PCHs limited by weak intermolecular forces, we designed a PCH with a dual-network framework comprising N-isopropylacrylamide-co-acrylamide (NIPAM-co-AM) and biomass lotus root starch (LR). Since LR is rich in hydroxyl groups, it can undergo molecular linkage entanglement with the NIPAM-co-AM hydrogel matrix, forming hydrogen bonds that significantly enhance the mechanical properties of the PCH. We have prepared PCH films capable of conveying multidimensional information about the extent and distribution of transient deformation by encapsulating magnetic photonic crystal microspheres (MPCMs) within a hydrogel matrix. The PCH films were found to have ultrafast response time (< 10 s), full-color tunable range, high spatial resolution, excellent mechanical toughness (tensile up to 0.17 MPa) and sensitivity (2.52 nm % −1 ), and were able to sense relative humidity (RH) from 11 % to 98 %. Equipped with a dynamically reconfigurable lattice, this dual-responsive (tensile/humidity) PCH not only facilitates the creation of water-rewritable photonic films but also holds promise for integration into structural color elastic fabrics, thereby presenting novel prospects for smart textile applications.
研究领域:
材料科学
·
生物工程
·
智能材料
·
纺织工程
·
光子学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2024
·
IF 5.5
Lingtao Wang,Ruiting Xu,Lingjie Meng,Qiuyang Zhang,Zheng Qian,Jie Chen,Changjiang Pan
Although magnesium alloy has received tremendous attention in biodegradable cardiovascular stents , the poor in vivo corrosion resistance and limited endothelialization are still the bottlenecks for its application in cardiovascular stents. Fabrication of the multifunctional bioactive coating with excellent anti-corrosion on the surface is beneficial for rapid re-endothelialization and the normal physiological function recovery of blood vessels. In the present study, a bioactive hydrogel coating was established on the surface of magnesium alloy by copolymerization of sulfobetaine methacrylate (SBMA) and acrylamide (AM) via ultraviolet (UV) polymerization, followed by the immobilization of fucoidan (Fu). The results showed that the as-prepared multifunctional hydrogel coating could enhance the corrosion resistance and the surface wettability of the magnesium alloy surface, endowing it with the ability of selective albumin adsorption; meanwhile, it could augment biocompatibility. The following introduction of fucoidan on the surface could further improve the hemocompatibility characterized by reducing protein adsorption , minimizing hemolysis, and preventing platelet aggregation and activation. Additionally, the immobilized fucoidan promoted endothelial cell (EC) growth, as well as up-regulated the expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO) in endothelial cells (ECs). Consequently, this research paves a novel approach to developing a versatile bioactive coating for magnesium alloy surfaces and lays a foundation in cardiovascular biomaterials .
研究领域:
材料科学
·
生物医学工程
·
心血管材料
·
表面工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 48
·8170-8179
·
IF 4.776
Yu Cheng,Chao Huang,Dian Yang,Kai Ren,Jie Wei
Bilayer-type hydrogel composites that respond to multiple stimuli provide a useful approach for manufacturing soft actuators and intelligent sensors. In this study, we propose two types of bilayer hydrogel composites (referred to as “N” type and “D” type). The “N” type and the “D” type separately consist of poly(N-isopropylacrylamide) (PNIPAM) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) bilayer hydrogels, with acrylamide (AM) as the co-monomer. The “N” type hydrogel composite exhibits oriented bending as temperature increases or as environmental salt concentration increases. The “D” type also presents oriented bending as temperature increases. Additionally, it demonstrates bending and changes color based on the pH of the surrounding solution, since it is doped with an acid-based pH-indicator. In a demonstration, we present several straight rods composed of a mixture of “N” and “D” type hydrogel composites that are able to morph into the letters “SOS” under environmental changes (temperature or pH). This can be used as a visual environmental indicator, or as an alarm. Furthermore, we show structures composed of a mixture of “N” and “D” composites imitating the flexible motions of a ballet dancer or a Tai Chi master. These mixed bilayer polymer composites may be used for applications in soft robotics, biomimetic devices, and environmental sensors.
研究领域:
材料科学
·
软体机器人
·
环境传感
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）