ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Junwei Su,Xianzhen Dong,Chao Xu,Zheng Wang,Changjiang Liu,Hongjun Yang,Dong Zhang,Aixi Yu
The multi-territory perforator flap is a widely used microsurgical technique for repairing skin and tissue defects in diabetes. In the diabetic microenvironment, oxidative stress and inflammation from reactive oxygen species (ROS) lead to compromised blood supply to the flap, resulting in challenges for survival. The common complication of multi-territory perforator flap is distal necrosis, which is primarily attributed to the Choke zone, the critical location characterized by delayed blood supply and inadequate neovascularization. To address this issue, a ROS-responsive MSL@Z/G hydrogel is developed by encapsulating metformin-Sr-L-Arg@ZIF-90 (MSL@Z) nanoparticles into gelatine methacrylamide (GelMA), enabling the release of metformin, Sr ions and NO. The enhanced deformation resistance and compressive strength properties of the MSL@Z/G hydrogel make it suitable for tissue reconstruction and drug delivery. Additionally, the MSL@Z/G hydrogel exhibits antioxidant and anti-inflammatory effects, thereby modulating the vascular microenvironment. In the dorsal multi-territory perforated flap model of type 2 diabetic rats, the MSL@Z/G hydrogel demonstrates the ability to alleviate inflammation and promote neovascularization of the Choke zone, reducing distal necrosis, which holds great promise for improving flap survival in diabetes.
研究领域:
生物材料学
·
组织工程学
·
糖尿病研究
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Jun Li,Yun-Jie Wei,Xian-Ling Yang,Wan-Xia Wu,Meng-Qian Zhang,Meng-Yang Li,Zu-E Hu,Yan-Hong Liu,Na Wang,Xiao-Qi Yu
To maximize the utilization and response to the high oxidative stress environment of tumor sites while avoiding the dilemma of enhancing reactive oxygen species (ROS) response in a single way, mitochondrial targeting combined with fluorescent self-reporting polymeric nanocarriers (1K-TPP and 2K-TPP) with grafted structures were synthesized via a chemoenzymatic method in a high yield to simultaneously enhance the drug delivery of endogenous ROS responses. 1K-TPP and 2K-TPP loaded doxorubicin (DOX) at a high content over 12% and formed homogeneous spherical micelles. In vitro, both of them showed promising high sensitivity (detection limit below 200 nM H2O2), fast response, and ratiometric fluorescent self-reporting properties (fluorescent enhancement more than 200 times) to ROS and excellent stability under physiological conditions, while achieving a rapid release of the DOX in response to 1 mM H2O2. Cell co-localization experiments exhibited that they had favorable mitochondrial targeting, and mitochondrial isolation experiments also confirmed that the TPP-modified 1K-TPP selectively accumulated nearly three times in mitochondria than that in total cells. The internalization of 1K-TPP and 2K-TPP into cancer cells was greatly improved by nearly 200% compared to that of unmodified control (1K-OH and 2K-OH) and also explored a unique energy-dependent endocytosis. Furthermore, stimulation of endogenous ROS enhanced the green fluorescence intensity (up to 51.4%) of the linked probe so as to destroy the internal structure of the nanocarriers, achieving self-reporting of the drug’s intracellular release and tracking of the intracellular location of nanocarriers. The cytotoxicity of DOX-loaded 1K-TPP and 2K-TPP in tumor cells with a higher ROS content showed statistical superiority to that of 1K-OH and 2K-OH, benefiting from the extremely good endogenous ROS response sensitivity leading to the differential selective release of drugs. These results demonstrate the potential of 1K-TPP and 2K-TPP, especially for 1K-TPP, as mitochondria-targeted, fluorescent self-reporting nanocarriers for combined enhancement of endogenous ROS responsiveness.
研究领域:
生物医学工程
·
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 44
·21235-21244
·
IF 3.925
Huan Xu,Mingyue Yang,Yijing Du,Tian Gao,Yi Liu,Liwei Xiong,Na Peng
Nano-drug carriers have been widely used in chemotherapy to improve the efficacy of chemotherapeutic drugs. Polymer nano-carriers have greater potential for the enrichment of chemotherapeutic drugs at the target tumor site and controlled release. Herein, a series of amphiphilic copolymers (ITT) was synthesized via melt polymerization with a ROS-cleavable thioketal cross-linker, imidazole groups, and polyethylene glycol-conjugated triphenylphosphonium (PEG-TPP) segments; the actual proportions of the imidazole groups to the PEG-TPP segments were 5.2 : 1, 2.6 : 1, and 1.8 : 1, respectively. The amphiphilic copolymers could self-assemble into cationic micelles with hydrophobic imidazole groups as the core and hydrophilic PEG-TPP segments as the shell in deionized water. The cationic micelles with an average particle size of 124.6–187.3 nm showed a drug loading content (DLC) of 5.65–6.10%. In vitro release studies revealed the pH/ROS dual-responsiveness of the DOX-loaded ITT micelles, and the release behavior of DOX from the micelles strongly depended on the content of imidazole groups in the ITT micelles. Typically, the release of the encapsulated DOX was 27.2%, 30.0%, and 34.1% from DOX-loaded ITT-1 micelles in PBS (pH 6.5) containing 0, 100, and 500 μM H2O2, respectively. The release of the encapsulated DOX was 20.3%, 27.2%, and 42.5% from DOX-loaded ITT-1 micelles in PBS (pH 7.4), PBS (pH 6.5), and PBS (pH 5.0), respectively. The DOX-loaded micelles effectively inhibited the growth of 4T1 cells through being internalized into the 4T1 cells and releasing DOX into the mitochondria, with a cell viability of less than 65% when the DOX concentration was 2.5 μg mL−1. This work presents a novel mitochondria-targeting and pH/ROS-responsive polymer nanocarrier for potential chemotherapy applications.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 9
·3706-3716
·
IF 5.251
Hang Liu,Wei Jiang,Qin Wang,Lifeng Hang,Yucai Wang,Yanmei Wang
Tumor hypoxia, which is indispensable to tumor propagation and therapy resistance, has been one of the most important factors influencing clinical outcomes. To modulate the hypoxia microenvironment, we herein developed reactive oxygen species (ROS)-sensitive arylboronic ester-based biomimetic nanocarriers co-encapsulated with a photosensitizer chlorin e6 (Ce6) and a hypoxia-activated prodrug tirapazamine (TPZp) for tumor-specific release and synergistic photodynamic chemotherapy. In order to bypass macrophage uptake and improve tumor penetration, the nanocarriers were further modified with the red blood cell membrane and iRGD peptide (denoted as NPs@i-RBMCe6+TPZp). After administration, NPs@i-RBMCe6+TPZp exhibited prolonged blood circulation, selective tumor accumulation and excellent penetration into the tumor interior. Upon light irradiation, ROS were generated by Ce6 for photodynamic therapy (PDT), which subsequently caused dissociation of the ROS-responsive nanocarriers. An enhanced therapeutic effect was further achieved through the activation of TPZp in the aggravated local hypoxia microenvironment. The synergistic cancer therapy based on NPs@i-RBMCe6+TPZp significantly suppressed tumor growth with negligible side effects. The biomimetic nanocarriers have great potential to overcome hypoxia-limited PDT, and significantly improve the anticancer efficacy by synergistic tumor-targeted PDT and hypoxia-activated chemotherapy.
研究领域:
癌症治疗
·
纳米医学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 51
·29711-29720
·
IF 3.049
Yan Zhang,Yunyun Wang,Yuxun Zhao,Wen Gu,Yongqiang Zhu,Shifa Wang
A series of novel camphor-based pyrimidine derivatives (3a–3x) have been synthesized; their structures were determined by using conventional methods and compound 3f was further confirmed through single crystal XRD analysis. The cytotoxic activity of the target compounds against a panel of human normal (GES-1) and cancer cell lines (MDA-MB-231, RPMI-8226, A549) was evaluated by MTS assay. Here we found that compound 3f exhibited the strongest anti-tumor activity, comparable to that of etoposide, and had much lower cytotoxicity to normal GES-1 cells (IC50 > 50 μM) than the reference drug (IC50 = 8.89 μM). Subsequent mechanism studies in MDA-MB-231 cells revealed that compound 3f caused G0/G1 phase arrest and apoptosis in a dose dependent manner. Moreover, the loss of mitochondrial membrane potential and enhancement of cellular ROS levels were also observed upon 3f treatment, which indicated that 3f exerted cytotoxic activity by a ROS-mediated mitochondrial apoptosis pathway. This result was confirmed by a significant increase in the expression of pro-apoptotic proteins Bax, cytochrome C and caspase-3, and downregulation of anti-apoptosis protein Bcl-2. Overall, 3f can be adopted for further investigation in the development of antitumor agents based on natural products.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Yunhao Ma,Xinran Dong,Ying Wang,Zhaoming Wang,Yong Xie,Wendi Zhang,Daodong Pan,Hui Zhou,Baocai Xu
Research conducted previously has demonstrated that apoptosis significantly influences the chicken quality. While ROS are acknowledged as significant activators of apoptosis, the precise mechanism by which they influence muscle cell apoptosis in the post-mortem remains unclear. In this study, chicken samples were treated with rosemarinic acid and H 2 O 2 to induce varying ROS levels, and the ROS-triggered apoptosis mechanism in chicken muscle cells in post-mortem was analyzed. The TUNEL results revealed that elevated ROS levels in chicken were associated with a greater degree of muscle cell apoptosis. Western-blot results suggested that sarcoplasmic ROS could initiate apoptosis through the mitochondrial pathway by activating the MAPK-JNK signaling pathway. Moreover, TEM and shear force results demonstrated that muscle cell apoptosis initiates myofiber fragmentation and structural damage to sarcomeres, ultimately reducing chicken tenderness. This study enhances our understanding of post-mortem muscle cell apoptosis, providing valuable insights for regulating chicken quality.
研究领域:
食品科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
2022
·
IF 1.496
Bozhan Tan,Zhiwen Qi,Guliang Yang,Haiyan Zhong
Tangeretin (Tan) possesses great anti-oxidation and anti-inflammation bioactivities; however, it is accompanied by poor water solubility, which leads to inefficient cellular internalization. To address this issue, a reactive oxygen species (ROS)-triggered poly (thioether-polyesters) micelle (PDHP, PEG-DTT) was designed and prepared via self-assembly, which consisted of poly (thioether-polyesters) as the hydrophilic shell, and the drug Tan as the hydrophobic inner core. The micelles (Tan@ PDHP), with a 63.15% loading efficiency of Tan, showed negligible cytotoxicity, high stability in phosphate-buffered saline buffer (pH = 7.4), and continuous release of Tan with the stimulation of H2O2. In addition, this Tan loading micelle was more efficient in responding to the formation of ROS in the lipopolysaccharide-stimulated RAW264.7 cells compared to that of the free Tan. In short, the strategy of encapsulating the low solubility Tan in ROS-triggered poly (thioether-polyesters) micelles provides an effective assay of enhancing Tan's antioxidative activity.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Shuangshuang Chen,Zelin Sang,Yumei Li,Hui Li,Zhenhua Chen,Xifan Mei,Xianbing Dai,Xiuli Ren
Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system. How to effectively deliver drugs to the site of spinal cord injury lesions through the blood spinal cord brain barrier (BSCB) has always been a challenge. There is an urgent need for developing a controllable and effective method to continuously release drug for SCI repair. Microneedles are a promising drug delivery method, however, how to control drug release smartly from microneedles remains a cutting-edge field. Herein, a NIR triggered photothermal responsive microneedles patch with Au@polyphenol nanospheres encapsulated was designed for SCI repair. By regulating the NIR irradiation, the thermal swelling rate of the microneedles can be precisely controlled. Therefore, the releasing of Au@polyphenol nanospheres from the microneedles could be controlled. Gold nanoparticles are known as nanozyme in photothermal therapy. Polyphenol nanospheres released from microneedles are helpful in promoting spinal cord injury repair by modulating mitochondrial ROS microenvironment. This NIR responsive microneedles array patch loaded with gold@polyphenol nanospheres has the advantages of effectively clearing reactive oxygen species, promoting mitochondrial autophagy, rebuilding redox balance, and reducing neuronal apoptosis.
研究领域:
生物医学工程
·
神经科学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yuxuan Dai,Shenghan Gao,Zhi Zhang,Wan-Jie Du,Xinyu Bao,Yun Xu
Alzheimer's disease (AD) has displayed complex pathological features, in which oxidative stress and ferroptosis play important roles. The development of collaborative treatment methods aimed at multiple pathological factors is particularly important for effective alleviation of AD. In our research, a multifunctional delivery system (CART-CeO 2 )@HA was developed for the co-delivery of neuroprotective Cocaine- and amphetamine-regulated transcript (CART) peptides and antioxidant CeO 2 nanozymes encapsulated within an ROS-responsive nanogel. Under the stimulation of Aβ, (CART-CeO 2 )@HA exhibited effective relief for cell apoptosis, mitochondrial dysfunction and synaptic loss on account of ROS removal and ferrous ions chelation. With sufficient accumulation and sustained drug release in the brain of APP/PS1 mice, (CART-CeO 2 )@HA significantly reduced the levels of oxidative stress and ferroptosis, which facilitate the reduction of Aβ deposition and the repair of neuronal damage, jointly rescuing the cognitive impairment in APP/PS1 mice. These results verified the clinical potential of the multi-target delivery system in AD synergistic therapy.
研究领域:
神经科学
·
纳米技术
·
药剂学
·
生物医学工程
·
病理学
✓ 已验证
产品关联
DOI
高影响因子
Applied Materials Today
·
2021
·
IF 10.041
Jihao Ruan,Qili Yu,Haomin Cui,Xing Qin,Limei Qin,Shuai Chen,Dechao Niu,Cunyi Fan
ABSTRACT Oxidative stress is considered an efficient therapeutic target in the progression of osteoarthritis (OA). Unfortunately, the current drug delivery system for the reactive oxidative species (ROS) scavengers is still unsatisfactory due to their insufficient responsiveness and rapid joint clearance. In this study, we design and develop a smart anti-oxidative agent by constructing a dual-responsive hybrid micelle with free radical scavenger melanin in the micellar core and polydopamine on the shell (designated as DHMP/M) for photoacoustic imaging-guided knee OA therapy. The resulting DHMP/M displays a unique long-term controlled-release behavior involving the slow and persistent release under endogenous ROS stimuli and short-burst release capability triggered by exogenous near-infrared (NIR) light. More importantly, DHMP/M possesses excellent free radical scavenging capacity and protective effects in chondrocytes in vitro and in in vivo rat OA models. Additionally, DHMP/M exhibits efficacious photoacoustic (PA) imaging for adjusting the therapy on demand. The RNA-Seq assay of rats further shows a significant reduction of TLR-2 in the OA cartilage, revealing that DHMP/M can protected OA from inflammation via TLR-2/MAPK/Akt signaling. Consequently, the present ROS/NIR dual-responsive melanin delivery platform together with PA imaging-monitoring provides a precise theranostic strategy for OA therapy.
研究领域:
药学
·
生物医学工程
·
治疗诊断学
·
成像科学
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Yanjuan Huang,Tao Zhang,Qin Wei,Zishan Zeng,Yujun Gong,Xiaoyu Xu,Meixu Chen,Chunshun Zhao
Posterior capsular opacification (PCO) is the leading cause of vision loss after cataract, mainly caused by the adhesion, proliferation and trans-differentiation of post-operative residual lens epithelial cells (LECs). Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades. Herein, we developed a “NIR-triggered ROS storage” intraocular implant (CTR-Py-PpIX) based on capsular tension ring (CTR), which is concurrently linked with photosensitizer protophorphyrin IX (PpIX) and energy storage 2-pyridone derivative (Py), to guarantee instantaneous and sustainable ROS generation for LECs killing, aiming to achieve more efficient and safer photodynamic therapy (PDT) to effectively prevent PCO. The silylated PpIX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-PpIX. Results demonstrated that CTR-Py-PpIX had dual functions of PDT and battery, in which PpIX could generate ROS extracellularly under irradiation, with one part directly inhibiting LECs by lipid peroxidation (LPO) induction of cell membranes. Meanwhile, the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed. Ultimately, the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions, achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility. This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.
研究领域:
眼科学
·
光动力疗法
·
生物医学工程
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-17
·
IF 9.429
Gu Jiayi,Wang Xueling,Chen Yuming,Xu Ke,Yu Dehong,Wu Hao
Background Excessive accumulation of reactive oxygen species (ROS) has been documented as the crucial cellular mechanism of cisplatin-induced ototoxicity. However, numerous antioxidants have failed in clinical studies partly due to inefficient drug delivery to the cochlea. A drug delivery system is an attractive strategy to overcome this drawback.Methods and resultsIn the present study, we proposed the combination of antioxidant astaxanthin (ATX) and ROS-responsive/consuming nanoparticles (PPS-NP) to combat cisplatin-induced ototoxicity. ATX-PPS-NP were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units, which scavenged ROS and disintegrate to release the encapsulated ATX. The ROS-sensitivity was confirmed by 1H nuclear magnetic resonance spectroscopy, transmission electron microscopy and an H2O2 ON/OFF stimulated model. Enhanced release profiles stimulated by H2O2 were verified in artificial perilymph, the HEI-OC1 cell line and guinea pigs. In addition, ATX-PPS-NP efficiently inhibited cisplatin-induced HEI-OC1 cell cytotoxicity and apoptosis compared with ATX or PPS-NP alone, suggesting an enhanced effect of the combination of the natural active compound ATX and ROS-consuming PPS-NP. Moreover, ATX-PPS-NP attenuated outer hair cell losses in cultured organ of Corti. In guinea pigs, NiRe-PPS-NP verified a quick penetration across the round window membrane and ATX-PPS-NP showed protective effect on spiral ganglion neurons, which further attenuated cisplatin-induced moderate hearing loss. Further studies revealed that the protective mechanisms involved decreasing excessive ROS generation, reducing inflammatory chemokine (interleukin-6) release, increasing antioxidant glutathione expression and inhibiting the mitochondrial apoptotic pathway.Conclusion sThus, this ROS-responsive nanoparticle encapsulating ATX has favorable potential in the prevention of cisplatin-induced hearing loss.Graphical Abstract
研究领域:
药学
·
纳米技术
·
耳科学
·
药物递送系统
·
抗氧化治疗
✓ 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）