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JOURNAL OF BIOMATERIALS APPLICATIONS · 2025 · IF 2.5

Development of a ROS-responsive, glutathione-functionalized injectable hydrogel system for controlled drug release

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
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Biomaterials Science · 2024 · IF 5.8

ROS-responsive thermosensitive polypeptide hydrogels for localized drug delivery and improved tumor chemoimmunotherapy

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.

CAS / MDL: 63-68-3
研究领域: 生物材料学 · 肿瘤免疫学 · 药剂学
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

ROS-Responsive Hydrogel Enables Drug/Ion/Gas Co-Delivery for Improving Survival of Multi-Territory Perforator Flap in Diabetes

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.

CAS / MDL: 760-93-0
研究领域: 生物材料学 · 组织工程学 · 糖尿病研究
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RSC Advances · 2024 ·Vol. 14 ·期 8 ·5577-5587 · IF 3.9

ROS-responsive polyprodrug micelles carrying suicide genes in combination with chemotherapy and gene therapy for prostate cancer treatment

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.

CAS / MDL: 2022-85-7 298-93-1
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
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Polymer Chemistry · 2018 ·Vol. 9 ·期 7 ·904-911 · IF 4.927

Facile synthesis of ROS-responsive biodegradable main chain poly(carbonate-thioether) copolymers

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.

CAS / MDL: 102-09-0
研究领域: 材料科学 · 生物医学工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

ROS-responsive carboxymethyl chitosan nanoparticles loaded with astaxanthin for alleviating oxidative damage in intestinal cells

Xiaoting Yu,Yannan Chen,Mingqian Tan

The controlled release of antioxidant substances at the intestinal oxidative damage site is crucial for alleviating intestine-related diseases. Herein, the novel ROS-responsive carrier was synthesized through simple amidation reaction between carboxymethyl chitosan (CMC) and methionine (Met), a natural organic compound containing ROS-responsive linkages (thioether). Initially, astaxanthin (AXT) nanoparticles (AXT 2 @CMT) with excellent stability and drug loading capacity (39.68 ± 0.23   μg/mL) were prepared by optimizing various reaction conditions. In the simulated high-concentration ROS environment of the intestine, CMT achieved a transition from hydrophobic groups (thioether) into hydrophilic groups (sulfone), which was conducive to the controlled release of AXT. In vitro cell experiments revealed that AXT 2 @CMT could effectively alleviate the oxidative damage in intestinal epithelioid cell line No. 6 (IEC-6 cell) caused by H 2 O 2 . This study achieved a straightforward preparation of ROS-responsive nanocarrier through food ingredients, offering a theoretical foundation for the controlled release of AXT at the intestinal oxidative damage site.

研究领域: 纳米技术 · 药学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOCONJUGATE CHEMISTRY · 2025 · IF 3.9

Synthetic Redox-Responsive Nanocomplexes Facilitate Spatially Controlled mRNA Release and Tumor-Selective Expression

Sheng Lin,Xia Cheng,Xiyi Chen,Jinxuan He,Wenxiu An,Qiufang Bai,Qixian Chen,Lie Ma,Jianhua Hu,Yue Wang,Xiabin Lan

The refinement of dynamic molecular mechanisms regulating mRNA release kinetics represents a critical frontier in advancing the synthetic mRNA delivery systems. This study details the synthesis of an intriguing ROS-responsive cationic block copolymer (pM-pBD) via reversible addition−fragmentation chain transfer (RAFT) polymerization, employing biocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC) and charge-reversible (2-acryloyl)ethyl(boronic acid benzyl)diethylammonium bromide (BD) as monomeric precursors. The synthesized copolymer facilitates electrostatic-driven self-assembly with anionic mRNA. Mechanistically, the pBD block exhibits ROS-mediated charge transition, enabling stimulus-dependent molecular decomposition and promoting mRNA payload liberation, thereby establishing spatial regulation of translational activity. Furthermore, intracellular ROS modulation experiments revealed that systemic ascorbic acid administration selectively enriches reactive oxygen species within tumor microenvironments. This redox microenvironment significantly amplifies pM-pBD nanocomplex-mediated mRNA expression by an order of magnitude across multiple carcinogenic cell lines, validating the ROS-responsive characteristics of our rationally designed delivery platform. In vivo studies demonstrated the highest mRNA expression levels in tumors when aided by ascorbic acid adjuvants, despite lower tumor accumulation of mRNA compared to renal and hepatic sequestration post intravenous administration of the pM-pBD nanocomplex. This spatial expression pattern correlates with ascorbic acid-mediated intratumoral ROS accumulation, which promotes cargo release and subsequent protein synthesis of approximately 6.4-fold enhancement. Our approach, integrating redox-responsive polymer design with organ-specific pharmacological modulation, signifies a transformative advancement in targeted nucleic acid delivery. By merging stimulus-responsive materials science with tumor microenvironment biology, this methodology provides a foundation for spatially controlled mRNA expression, presenting an innovative strategy for precision oncology applications.

CAS / MDL: 623-05-2
研究领域: 生物材料 · 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
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JOURNAL OF CONTROLLED RELEASE · 2023 · IF 10.8

Tumor permeable self-delivery nanodrug targeting mitochondria for enhanced chemotherapy

Guiping Yuan,Yifan Zhang,Shiqun Shao,Zhuxian Zhou,Jianbin Tang,Jiajia Xiang,Youqing Shen

Drug self-delivery systems (DSDSs) have been extensively exploited to enhance drug loading capacity and avoid excipient-related toxicity issues. However, deficient tumor targeting, inferior tumor permeability, prominent burst release, and nonspecific subcellular distribution remain major obstacles. Herein, we reported a ROS-responsive amphiphilic prodrug (CPT-S-NO) synthesized by the conjugation of zwitterionic tertiary amine-oxide (TAO) moiety and hydrophobic camptothecin (CPT) through a thioether linkage, which formed a nanoparticulate DSDS in an aqueous solution. CPT-S-NO, compared with CPT-11 and the water-soluble TAO-modified CPT prodrug (CPT-NO), exhibited prolonged blood circulation, enhanced tumor accumulation, deep tumor penetration, efficient mitochondrial targeting, and ROS-activated drug release to induce mitochondrial dysfunction, corporately conducing to the superior antitumor efficacy in vivo. This TAO decoration strategy promises potential applications in designing multipotent DSDSs for various drugs.

研究领域: 药理学 · 肿瘤学 · 纳米医学 · 生物化学
✓ 已验证 DOI PubMed 高影响因子
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Nano Today · 2025 · IF 10.9

In situ oxidation-responsive nanovaccine coordinates photosensitizer and STING agonist for cancer photo-immunotherapy

Zhaochu Xu,Jiang Yu,Yingxi Zhang,Yue Wang,Wenxiao Li,Baoyue Zhang,Wenwen Cui,Yicheng Li,Yue Wang,Zimeng Yang,Yubo Liu,Xin Li,Yongjun Wang,Zhonggui He,Hongzhuo Liu

Cancer vaccine has emerged as a promising therapeutic paradigm for cancer therapy. However, the lack of tumor-associated antigens and abundant immunosuppressive factors seriously diminish the efficacy of immunotherapy, resulting in poor clinical benefits. In this report, we engineered a coordinated immunostimulatory nanoplatform, termed MP@PPS NPs, by physically combining reactive oxygen species (ROS)-responsive poly (propylene sulfide) nanoparticles loaded with the photosensitizer pyropheophorbide a (PPa) and stimulator of interferon genes (STING) agonist (MSA-2), to function as an in situ cancer vaccine to amplify immunotherapeutic outcomes. Excellent stability of MP@PPS NPs endowed prolonged drug circulation time and improved tumor accumulation, while their small size boosted deeper drug penetration within tumors. Crucially, upon laser irradiation, the MP@PPS NPs could generate abundant ROS, which induced tumor ablation, triggered immunogenic cell death to initiate an adaptive antitumor immune response and facilitated the local release of MSA-2, thereby promoting innate antitumor immunity through the cGAS-STING pathway. MP@PPS NPs markedly suppressed both primary and distant tumor progression, promoted dendritic cell maturation and increased cytotoxic T lymphocyte infiltration, elicited robust antitumor immunity. Meanwhile, MP@PPS NPs treatment impeded the lung metastatic in conjunction with anti-PD-L1 treatment. This work holds significant promise for the synergistic photodynamic immunotherapy, and offers a crucial inspiration for addressing the problems of insufficient antitumor immunity and ineffective cancer treatments.

CAS / MDL: 141-52-6 51376-18-2
研究领域: 肿瘤学 · 免疫学 · 纳米医学
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ACS Applied Bio Materials · 2020 · IF 0

Dual-Responsive Dual-Drug-Loaded Bioinspired Polydopamine Nanospheres as an Efficient Therapeutic Nanoplatform against Drug-Resistant Cancer Cells

Yiyan Song,Ping Zhu,Zhihui Xu,Jin Chen

Multidrug resistance evoked by overusing pharmaceuticals of poor water solubility has posed a serious threat to public health, which urges the development of safe and efficacious therapeutic formulations. In this study, biomimetic nanospherical polydopamine (PDA) formed under mild conditions was modified using methoxypolyethylene glycol amine (m-PEG-NH2) to produce a polydopamine-based drug delivery platform. As characterized by various physicochemical methods, the PEGylated PDA with a uniform size distribution showed superior biocompatibility and efficient load capability for two hydrophobic anticancer drugs of paclitaxel and phytochemical curcumin, which exhibited synergistic cytotoxicity and a pH/ROS-responsive release behavior. Significantly, an enhanced effect of the encapsulated paclitaxel and curcumin was identified toward the drug-resistant A549/TAX cancer cells, which was correlated with the improved cellular internalization of hyperbranched PDA composites and distinctive cell cycle arrest of loaded drugs. The dual-drug-loaded spherical PDA nanocomposites hold enormous potential to tackle drug resistance from a chemotherapy perspective.

研究领域: 药学 · 纳米技术 · 肿瘤学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2020 · IF 4.389

ROS triggered cleavage of thioketal moiety to dissociate prodrug nanoparticles for chemotherapy

Qingqing Pan,Xin Deng,Wenxia Gao,Jing Chang,Yuji Pu,Bin He

With the utilization of high concentration reactive oxygen species (ROS) in tumor microenvironment, PEG-doxorubicin (PEG-DOX) prodrug was synthesized via a thioketal moiety as the linker, which was ROS cleavable to trigger DOX release from the self-assembled prodrug nanoparticles. The in vitro ROS sensitivity of prodrug nanoparticles (NPs) was investigated in Fenton agent and H 2 O 2 , and the disassembly of NPs was more sensitive to Fenton reagent. After internalized in HepG2 cells via endocytosis, the cellular ROS consuming test revealed intracellular DOX release. The pharmacokinetics and biodistribution study demonstrated that the in vivo elimination of NPs was significantly improved and the NPs were passively targeted to tumor tissues via EPR effect. The ROS-responsive prodrug NPs exhibited excellent antitumor activity in HepG2 tumor-bearing nude mice, remarkably induced tumor cells apoptosis and reduced the systemic toxicity of DOX. Our study revealed the ROS responsive prodrug nanoparticle is an effective strategy to fabricate nanomedicine for cancer chemotherapy.

研究领域: 药物递送系统 · 肿瘤学 · 生物材料
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Materials Today Bio · 2025 · IF 10.2

Multi-stage cooperative ROS-responsive hydrogel platform for drug delivery in myocardial ischemia-reperfusion injury repair

Qiao Luo,Nianlan Cheng,Yongqing Yang,Ni Shao,Tianqi Nie,Jifeng Chen,Cuiqing Huang,Siqi Zhang,Yanyu Huang,Chon Man Ieong,Xiaokai Zhang,Kuan Hu,Zeyu Xiao,Liangping Luo

Myocardial ischemia-reperfusion (I/R) injury is characterized by oxidative stress, mitochondrial dysfunction, inflammation, and fibrosis, ultimately leading to chronic cardiac dysfunction and heart failure. Current therapeutic strategies that predominantly target single biological pathways exhibit limited long-term efficacy, underscoring the necessity for multi-targeted approaches. In this study, we developed a ROS-responsive hydrogel system, S1&FT/Lipo-QCFT, tailored to deliver drugs for treating various stages of myocardial I/R injury. This system timing of drug release to achieve rapid deployment at early intervention stages and maintain sustained release thereafter. Initially, the hydrogel platform quickly releases the molecular forms of the superoxide inhibitor S1QEL1.1 and tannic acid, specifically targeting the elevated ROS levels at the I/R site to alleviate early oxidative damage and encourage macrophage polarization toward the M2 phenotype. Subsequently, the system gradually releases anti-fibrotic agent FT011, encapsulated in lipid nanocarriers, which actively counters TGF-β1-induced fibrosis and forestalls adverse ventricular remodeling, thereby enhancing long-term cardiac repair. In vivo studies demonstrated that the S1&FT/Lipo-QCFT hydrogel significantly improved cardiac function and reduced adverse ventricular remodeling. This hydrogel system provides a promising multi-targeted therapeutic strategy for comprehensive myocardial I/R injury treatment with strong potential for clinical translation.

研究领域: 药理学 · 心血管医学 · 生物材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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