Nanoscale
·
2023
·
IF 6.7
Yu Ran,Shanmei Yin,Pei Xie,Yaxue Liu,ying wang,Zongning Yin
Acute Lung Injury (ALI) is an inflammatory disease caused by multiple factors such as infection, trauma, and chemicals. Without effective intervention during the early stages, it usually quickly progresses to acute respiratory distress syndrome (ARDS). Since ordinary pharmaceutical preparations cannot precisely target to the lungs, their clinical application is limited. In response, we constructed a γ3 peptide-decorated and ROS-responsive nanoparticle system encapsulating therapeutic dexamethasone (Dex/PSB-γ3 NPs). In vitro, Dex/PSB-γ3 NPs had rapid H2O2 responsiveness, low cytotoxicity, and strong intracellular ROS removal capacity. In a mouse model of ALI, Dex/PSB-γ3 NPs accumulated at the injured lung rapidly, alleviating pulmonary edema and cytokine levels significantly. The modification of NPs by γ3 peptide achieved highly specific positioning of NPs in the inflammatory area. The ROS-responsive release mechanism ensured the rapid release of therapeutic dexamethasone at the inflammatory site. This combined approach improves treatment accuracy, and drug bioavailability, and effectively inhibits inflammation progression. Our study could effectively reduce the risk of ALI progressing to ARDS and hold potential for the early treatment of ALI.
研究领域:
药理学
·
纳米技术
·
炎症
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE
·
2025
·
IF 3.6
Sunqi Yu,Siyuan Chen,Tianrui Tong,Yunfeng Yan,Qi Shuai
Micelle-based drug delivery systems (DDS) have emerged as a promising solution to address challenges associated with the in vivo delivery of hydrophobic anticancer chemotherapeutics. However, micelles still encounter issues such as drug pre-leakage and poor stability in physiological conditions. To overcome these limitations, we developed a core-cross-linking strategy utilizing amphiphilic copolymers, mPEG- b- P(AVL- co -LA) (mPPAL), functionalized with phenylboronic acid (PBA), and catechol by CuAAc “click” chemistry, respectively. These copolymers self-assembled into core-cross-linked micelles (CLMs), featuring boronic ester bonds, which were characterized through a series of evaluations. The CLMs exhibited a rational particle size, uniform morphology, low critical micelle concentration (CMC), high PTX loading capacity, and excellent stability. Two promising micelles, CLM1 and CLM3, were identified, and their responsiveness to acidic pH and elevated levels of ROS was confirmed to enable controlled PTX release. The results of MTT assay and hemolytic analysis demonstrated high biocompatibility and potential in vivo application of these selected CLMs. The anticancer efficacy of the selected PTX-CLMs was further validated through MTT assay and 3D tumor spheroid studies. Fluorescence microscopy and flow cytometry demonstrated rapid intracellular uptake of the CLMs. In vivo biodistribution studies demonstrated successful accumulation in the targeted tumor tissue. These findings suggest that the boronic ester-based CLMs developed in this study are a promising nanocarrier for effective PTX delivery. Graphical Phenylboronic acid (PBA) and catechol-modified amphiphilic copolymers (mPPAL@R) were synthesized via ring-opening polymerization followed by CuAAc click chemistry. These copolymers were employed to construct pH- and ROS-dual-responsive micelles with boronic ester core-crosslinking. A series of in vitro and in vivo experiments were conducted to evaluate PTX-loaded micelles, demonstrating their significant potential for effective PTX delivery.
研究领域:
药剂学
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 11
·2145
·
IF 7.675
Yuanfang Chen,Yuwei Yang,Haikang Tang,Ziqi Zhang,Xiaoliang Zhou,Wenqing Xu
Radiation exposure can immediately trigger a burst of reactive oxygen species (ROS), which can induce severe cell death and long-term tissue damage. Therefore, instantaneous release of sufficient radioprotective drugs is vital to neutralize those accumulated ROS in IR-exposed areas. To achieve this goal, we designed, synthesized, and evaluated a novel oral ROS-responsive radioprotective compound (M1) with high biocompatibility and efficient ROS-scavenging ability to act as a promising oral drug for radiation protection. The compound is stably present in acidic environments and is hydrolyzed in the intestine to form active molecules rich in thiols. M1 can significantly remove cellular ROS and reduce DNA damage induced by γ-ray radiation. An in vivo experiment showed that oral administration of M1 effectively alleviates acute radiation-induced intestinal injury. Immunohistochemical staining showed that M1 improved cell proliferation, reduced cell apoptosis, and enhanced the epithelial integrity of intestinal crypts. This study provides a promising oral ROS-sensitive agent for acute intestinal radiation syndrome.Keywords:ROS response;aminothiols;oral administration;radioprotection;intestinal damage
研究领域:
药理学
·
放射生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Ping-fu Huang,Miaomiao Ma,Hao Wu,Wen-min Niu,Lu-lu Liu,Jia-bing Tong
Purpose Rheumatoid arthritis (RA) is an autoimmune disease with systemic inflammatory. Ibuprofen (IBF) and curcumin (CUR) were the commonly therapeutic ingredients for RA treatment and the combination administration possessed the ideal efficacy, however, the low solubility and lack of targeting produced the significant obstacles for the treatment. Methods In this study, the IBF prodrug decorated with the CD44 receptors and ROS-sensitive was prepared and encapsulated with the CUR named CUR@HA-TK-IBF were designed, the characterization of CUR@HA-TK-IBF were performed in vitro and the efficacity effect were evaluated using collagen induced arthritis (CIA) model. Results The obtained product CUR@HA-TK-IBF exhibited the diameter of 137.3 ± 4.5 nm, and the morphology of the nanoparticles showed the sphericity via the TEM. In vitro release results indicated that the IBF and CUR could slowly release in the normal environment and quickly release at the H 2 O 2 environment. Furthermore, the combination of CUR and IBF could significantly decrease the expression of the proinflammatory factors and the concentration of ROS and COX-2 in vitro . The animal experiment indicated that the CUR@HA-TK-IBF could alleviate the foot tumefaction and decrease the expression of proinflammatory factors in the RA model mice. Conclusion The CUR@HA-TK-IBF developed the new approach for co-deliver the IBF and CUR, which provided a new therapeutic strategy for the treatment of RA.
研究领域:
药学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2025
·
IF 2.5
Kai Hu,Linlin Liang,Jian Song
Oxidative stress arises from an imbalance between excessive production of reactive oxygen species (ROS) and the body’s antioxidant defenses. In neurodegenerative diseases, this imbalance leads to ROS accumulation, causing neuronal dysfunction and cell death. Traditional drug therapies often fail to address the dynamic nature of neuroinflammation, limiting their therapeutic efficacy. To overcome this challenge, we have developed an innovative ROS-responsive injectable hydrogel. This hydrogel is designed to detect oxidative stress sensitively and release glutathione in a controlled manner, thereby modulating inflammation and restoring the damaged immune microenvironment to facilitate tissue repair. The hydrogel was synthesized by crosslinking polyvinyl alcohol (PVA) with sodium alginate modified with 3-aminophenylboronic acid (Alg-PBA). We investigated the hydrogel’s formation mechanism and analyzed how component variations affect its morphological and rheological properties. Our findings demonstrate that an optimal Alg-PBA to PVA weight ratio of 2:1 yields a hydrogel with superior mechanical strength. Glutathione (GSH) release studies confirmed the hydrogel’s pronounced ROS-responsive drug release behavior. Furthermore, biocompatibility assessments revealed that the hydrogel loaded with 100 μg/mL GSH exhibited excellent compatibility and significantly inhibited neuronal apoptosis under oxygen-glucose deprivation (OGD) conditions. This work presents a promising strategy for treating inflammation-related diseases and provides valuable insights for designing next-generation hydrogels that adapt to injury-responsive microenvironments.
研究领域:
生物材料学
·
药剂学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Fujiang Li,Junfeng Ding,Zhenyu Li,Yan Rong,Chaoliang He,Xuesi Chen
In this study, we developed a ROS-responsive thermosensitive poly(ethylene glycol)-polypeptide hydrogel loaded with a chemotherapeutic drug, doxorubicin (Dox), an antiviral imidazoquinoline, resiquimod (R848), and the antibody targeting programmed cell death protein 1 (aPD-1) for local chemoimmunotherapy. The hydrogels demonstrated controllable degradation and sustained drug release behavior according to the concentration of ROS in vitro. Following intratumoral injection into mice bearing B16F10 melanoma, the Dox/R848/aPD-1 co-loaded hydrogels effectively inhibited tumor growth, prolonged animal survival time and promoted antitumor immune responses with low systemic toxicity. In the postoperative model, the Dox/R848/aPD-1 co-loaded hydrogels exhibited enhanced tumor recurrence prevention and long-term immune memory effects. Thus, the hydrogel-based local chemoimmunotherapy system demonstrates potential for effective antitumor treatment and prevention of tumor reoccurrence.
研究领域:
生物材料学
·
肿瘤免疫学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
RSC Advances
·
2024
·Vol. 14
·期 8
·5577-5587
·
IF 3.9
Kai Li,Sinan Tian,Ke Sun,Qingguo Su,Yanhui Mei,Wenjie Niu
Prostate cancer is the most common malignant tumor in the male reproductive system, and its incidence increases with age. Chemotherapy is one of the main strategies for treating prostate cancer, but it often comes with unavoidable side effects. Nanocarriers can improve drug utilization and targeting, and cationic carriers can also carry nucleic acids for gene therapy. In this study, we prepared a cationic micelle constructed from a polyprodrug that can deliver both chemotherapeutic drugs and nucleic acids simultaneously. The typical chemotherapeutic drug hydroxycamptothecin (HCPT) was linked by reactive oxygen species (ROS)-responsive coupling agents and forms amphiphilic block polymers with low molecular weight polyethyleneimine (PEI). The resulting cationic micelles can be triggered by high levels of ROS in tumor cells and collapse to release HCPT and suicide genes to kill tumor cells. At the same time, it reduces the killing of normal cells. In prostate cancer cells, it has been confirmed that the co-delivery carriers combined with chemotherapy and a suicide gene prodrug system have shown an ideal therapeutic effect on prostate cancer.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
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
Polymer Chemistry
·
2018
·Vol. 9
·期 7
·904-911
·
IF 4.927
Bingkun Yan,Yan Zhang,Chao Wei,Yue Xu
Oxidation-responsive thioether-functional polymers have emerged as potential materials for biomedical applications. Herein, we report the straightforward synthesis of a well-defined biodegradable thioether-containing polycarbonate (mPEG-b-PS) based on the macrocyclic sulfur-substituted carbonate monomer (MS) using an enzyme-catalyzed ring-opening polymerization with the thioether groups situated on the backbone. NMR, FTIR and GPC techniques were employed to confirm the structure of the copolymers. Moreover, the thioether groups endowed the copolymers with rich ROS responsiveness and the oxidation mechanism was clarified according to in situ1H-NMR, FTIR and TGA data. In addition, the water contact angles testified that the hydrophilicity of the copolymers was greatly improved during the H2O2 triggered oxidation process. The thioether oxidation to polar sulfone and sulfoxide groups enabled us to tailor the copolymer's solubility profile; thus, the size, morphology and transmittance of the nanostructure changed according to the results obtained using DLS, TEM and UV techniques. Furthermore, CCK-8 assays showed that the thioether-containing polycarbonate and their oxidized products were non-toxic up to a tested concentration of 250 μg mL−1. Moreover, the mPEG-b-PS had a definite H2O2-triggered drug release behaviour. Therefore, these results highlight a facile synthesis of biodegradable thioether-containing polymers and provide a novel ROS responsive material platform for further cancer therapy and inflammation targeting.
研究领域:
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Nanomaterials
·
2021
·Vol. 11
·期 11
·2875
·
IF 5.076
Yi-Mei Zhang,Meng Xia,Rui Ao,Li-Xia Gao,Yan Tang,Jiu-Hong Huang,Ya-Fei Luo,Zhong-Zhu Chen,Bo-Chu Wang,Zheng Huang
Mitochondria, as the powerhouse of most cells, are not only responsible for the generation of adenosine triphosphate (ATP) but also play a decisive role in the regulation of apoptotic cell death, especially of cancer cells. Safe potential delivery systems which can achieve organelle-targeted therapy are urgently required. In this study, for effective pancreatic cancer therapy, a novel mitochondria-targeted and ROS-triggered drug delivery nanoplatform was developed from the TPP-TK-CPI-613 (TTCI) prodrug, in which the ROS-cleave thioketal functions as a linker connecting mitochondrial targeting ligand TPP and anti-mitochondrial metabolism agent CPI-613. DSPE-PEG2000 was added as an assistant component to increase accumulation in the tumor via the EPR effect. This new nanoplatform showed effective mitochondrial targeting, ROS-cleaving capability, and robust therapeutic performances. With active mitochondrial targeting, the formulated nanoparticles (TTCINPs) demonstrate much higher accumulation in mitochondria, facilitating the targeted delivery of CPI-613 to its acting site. The results of in vitro antitumor activity and cell apoptosis revealed that the IC50values ofTTCINPs in three types of pancreatic cancer cells were around 20~30 µM, which was far lower than those of CPI-613 (200 µM); 50 µMTTCINPs showed an increase in apoptosis of up to 97.3% in BxPC3 cells. Therefore, this mitochondria-targeted prodrug nanoparticle platform provides a potential strategy for developing safe, targeting and efficient drug delivery systems for pancreatic cancer therapy.Keywords:mitochondria-targeting;ROS-responsive;drug delivery;nanoparticles;pancreatic cancer therapy;CPI-613
研究领域:
癌症治疗
·
药学科学
·
纳米技术
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Hong-Li Wang,ChuanMing Yu,Qiangling Yin,Jin-Wei Bu,Shuang Feng,Di Ning,Shu-Lin Liu,Linlin Liu,Zhi-Gang Wang
Drug therapy is an important measure to reduce the morbidity and mortality of influenza. However, small molecule drugs have inherent limitations, such as poor water solubility, non-specific biological distribution, and susceptibility to degradation during blood circulation, which impose a great burden on patients, both physically and mentally. Inspired by the high levels of reactive oxygen species (ROS) at the site of influenza A virus (IAV) infection, we have developed an intelligent responsive virus-mimicking nanodrug (Zana@HA-Lip) based on a biomimetic approach, reduces the damage of the drug to normal tissues or organs while achieving the purpose of antiviral therapy by precisely releasing the drug at the lesion site. Zana@HA-Lip offers distinct advantages regarding lesion site tropism, duration of action, and efficiency of release in response to ROS. This work not only presents a safe and effective strategy for alleviating lung injury caused by IAV infection but also introduces a new concept for the precise customization of virus-mimicking nanocarriers.
研究领域:
药剂学
·
纳米技术
·
病毒学
·
生物医学工程
·
靶向治疗
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）