LANGMUIR
·
2025
·
IF 3.9
Mi Liu,Weidan Zhao,Denghao Li,Dingyu Cui,Jiali Liu,Qingao Chen,Yan Zhou,Li Jiang,Huaibin Zhou
Infected wound healing remains a significant clinical challenge due to bacterial resistance and excessive inflammation. Herein, a multifunctional hydrogel dressing (Nb2C-Arg/Gel) is developed that integrates two-dimensional Nb2C nanosheets (photothermal agent) and arginine [nitric oxide (NO) donor] into a calcium ion cross-linked sodium alginate matrix. The hydrogel has a relatively high swelling capacity and good ability to scavenge reactive oxygen species (ROS), which are beneficial for absorbing wound exudate and reducing the inflammatory response of wounds. Under irradiation with a low-power NIR-II laser (1064 nm, 1 W cm–2), Nb2C-Arg/Gel achieves rapid photothermal heating (48.6 °C in 1 min), while thermally enhances arginine decomposition-triggered on-demand NO release. This synergistic mechanism provides superior antimicrobial efficacy against Staphylococcus aureus (97.65%) and methicillin-resistant S. aureus (90.05%). In vivo studies on MRSA-infected murine wounds demonstrate that the residual area on day 10 was 2.9%, which accelerated healing compared to that of the control group (17.8%), accompanied by reduced inflammation and enhanced angiogenesis. The excellent biocompatibility of hydrogel is validated by low hemolysis (<5%) and promoted fibroblast proliferation (125% cell viability). Combining with photothermal, NO-mediated antibacterial action, and ROS scavenging to alleviate oxidative stress, this antibiotic-free hydrogel dressing has great potential for clinical application for the treatment of refractory-infected wounds.
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BIOMACROMOLECULES
·
2025
·
IF 5.4
Fen Zheng,Shanming Zhang,Dongxuan Liu,Yitong Chen,Long Xu
Suboptimal intratumoral penetration remains a major obstacle to the clinical translation of nanomedicines, underscoring the need for innovative nanoplatforms that enable precise tumor penetration. While tumor-penetrating peptides are commonly used to improve nanomedicine accumulation and permeability in tumors, their efficacy in hypoxic regions remains limited. Herein, four pH/ROS dual-responsive polymer prodrugs, modified with or without the tumor-penetrating peptide CRGDK and the CAIX ligand, were constructed. The stability, pH/ROS responsiveness, in vitro drug release properties, and cellular uptake of the resulting micelles were evaluated. Tumor penetration was investigated using multicellular tumor spheroids (MTSs) and the PANC-1 xenograft model. Antitumor efficacy was studied in normoxic and hyperoxic cells, MTSs, and the xenograft model. Results showed that the NRP-1/CAIX dual-targeted prodrug micelles (P1) achieved deep tumor penetration in hypoxic tumor regions. A sequential targeting strategy employing both a tumor-penetrating peptide and a CAIX ligand offers a promising approach for enhancing nanomedicine infiltration into deep tumor areas.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Yating Sun,Qi Miao,Guanxin Zhao,Shengqi Wang,Min Liu,Xiuli Zhao,Jiulong Zhang
Diabetic wound (DW) is characterized by chronic inflammation and bacterial infection, making its healing a continuing clinical challenge. Herein, a living bacteria-loaded oxidized dextran hydrogel is successfully fabricated to accelerate wound healing via regulating inflammatory factors. Lactobacillus bulgaricus (LB), as a live microorganism, is encapsulated in the hydrogel via microcapsule technology with gelatin as a substance to reduce secondary infections and ensure the survival of LB. Gelatin microcapsules and oxidized dextran were used to prepare a pH/ROS responsive hydrogel (OPM@GLB) through a Schiff base reaction. Furthermore, mangiferin was also incorporated into the hydrogel by a dynamic borate ester bond to support desirable nutrition for LB. In vitro and in vivo results showed that the OPM@GLB hydrogel exhibited significant antibacterial and anti-inflammatory properties and promoted angiogenesis and collagen deposition to accelerate diabetic wound healing. This study may offer new insights for treating diabetic wound in the clinic.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Bin Liu,Shiqiao Rui,Donglin Bian,Jiahui Wang,Shuaipeng Feng,Zhu Liu,Yuanqi Yang,Wanqing Gong,Long Wan,Junyan Zhang,Qinfu Zhao
Carbon dots with dual enzyme-like activities of SOD and CAT-like were synthesized. • An orally administered precursor solution underwent ROS-responsive gelation at sites of colonic inflammation. • Inverting M1/M2 macrophage imbalance and recruiting Treg cells to drive immune responses. • Restoring intestinal integrity and rebalancing the gut microbiota. Inflammatory bowel disease (IBD) involves a complex inflammatory environment marked by excessive oxidative stress, impaired barrier function, and microbial imbalance. These interconnected pathologies are difficult to address with conventional single-target therapies. To tackle these challenges, this study developed an intelligently responsive oral hydrogel delivery system based on sulfur-doped ginger carbon dots (SGCDs). SGCDs, synthesized via a hydrothermal method, not only exhibited remarkable antioxidant capacity but also demonstrated multiple enzyme-like activities, including SOD-like and CAT-like, along with stable fluorescence imaging properties. Simultaneously, thiolated hyaluronic acid (HS 1:6 ), exhibiting ROS-responsive gelation properties, was synthesized via chemical modification and employed as the gel matrix. The oral precursor system (HS 1:6 @SGCDs), constructed by loading SGCDs into the HS solution, underwent ROS-triggered in situ gelation upon reaching the colonic inflammatory region. This transformation formed a physical barrier, prolonged retention time, and enabled controlled release of SGCDs. This system significantly alleviated pathological symptoms through multiple mechanisms, including efficient scavenging of excessive ROS, modulation of the immune microenvironment, amelioration of intestinal barrier dysfunction, and amelioration of dysbiosis with a trend toward recovery of a more balanced microbial community. Through disease-directed and source-based innovation, the system combined targeted material design with multifunctional therapeutic capabilities. Thus, HS 1:6 @SGCDs provided an innovative and comprehensive solution for the treatment of IBD.
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Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Ding Wenbin,Zhou Qirong,Lu Yifeng,Wei Qiang,Tang Hao,Zhang Donghua,Liu Zhixiao,Wang Guangchao,Wu Dajiang
Stem cell-based therapy has drawn attention as an alternative option for promoting prosthetic osteointegration in osteoporosis by virtue of its unique characteristics. However, estrogen deficiency is the main mechanism of postmenopausal osteoporosis. Estrogen, as an effective antioxidant, deficienncy also results in the accumulation of reactive oxygen species (ROS) in the body, affecting the osteogenic differentiation of stem cells and the bone formation i osteoporosis. In this study, we prepared a ROS-scavenging hydrogel by crosslinking of epigallocatechin-3-gallate (EGCG), 3-acrylamido phenylboronic acid (APBA) and acrylamide. The engineered hydrogel can scavenge ROS efficiently, enabling it to be a cell carrier of bone marrow-derived mesenchymal stem cells (BMSCs) to protect delivered cells from ROS-mediated death and osteogenesis inhibition, favorably enhancing the tissue repair potential of stem cells. Further in vivo investigations seriously demonstrated that this ROS-scavenging hydrogel encapsulated with BMSCs can prominently promote osteointegration of 3D printed microporous titanium alloy prosthesis in osteoporosis, including scavenging accumulated ROS, inducing macrophages to polarize toward M2 phenotype, suppressing inflammatory cytokines expression, and improving osteogenesis related markers (e.g., ALP, Runx-2, COL-1, BSP, OCN, and OPN). This work provides a novel strategy for conquering the challenge of transplanted stem cells cannot fully function in the impaired microenvironment, and enhancing prosthetic osteointegration in osteoporosis.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
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IF 5.518
Asim Mushtaq,Han Zhang,Mingyue Cui,Xiaoqing Lin,Shuqi Huang,Zhe Tang,Yike Hou,M. Zubair Iqbal,Xiangdong Kong
Magnetite hydroxyapatite nanoparticles show notable multifunctional therapeutic features in nanomedicine . However, designing MHAp nanoparticles with optimum dimensions, good stability and biocompatibility for specific biomedical applications is still in its infancy. Herein, a facile approach was employed to prepare ROS-responsive chlorin e6 and silk fibroin-loaded ultrathin magnetic hydroxyapatite nanorods for T 1 -magnetic resonance imaging and photodynamic therapy. Specifically, the Fe 3 O 4 -HAp nanorods were synthesized by the hydrothermal method , and then Pluronic® F-127 was used to improve the aqueous dispersion, biocompatibility, and loading capacity. Moreover, silk fibroin protein was encapsulated by a tri-block copolymer with good loading efficiency. Finally, the theranostic nano-assembly MHNRs-SF-Ce6 was completed by the addition of Ce6. The prepared MHNRs demonstrated excellent biocompatibility, cellular uptake, and ROS generation ability in in vitro after 660 nm laser irradiation, leading to the apoptosis of 4T1 mouse breast cancer cells. Notably, the designed MHNRs exhibited excellent r 1 relaxivity value and T 1 magnetic resonance imaging in vitro due to their minimal width (2 nm) of nanorods. Therefore, the obtained MHNRs-SF-Ce6 self-assembled nanoparticles provide an effective strategy for cancer diagnosis and photodynamic therapy.
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Acta Biomaterialia
·
2022
·
IF 10.633
Zhixuan Huang,Kun Qian,Jin Chen,Yao Qi,Yifeng E,Jia Liang,Liang Zhao
Zeolite-based nanomaterials have a large number of applications in the field of medicine due to their high porosity, biocompatibility and biological stability. In this study, we designed cerium (Ce)-doped Linde Type A (LTA) zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme to reduce dysfunction of the neurovascular unit (NVU) and attenuate cerebral ischaemia-reperfusion (I/R) injury. Owing to its unique adsorption capacity and mimetic catalytic activities , [email protected] adsorbed excess zinc ions and exhibited scavenging activity against reactive oxygen species (ROS) induced by acute I/R, thus reshaping the oxidative and zinc microenvironment in the ischaemic brain. In vivo results demonstrated that [email protected] significantly reduced ischaemic damage to the NVU by decreasing the infarct area, protecting against breakdown of the blood–brain barrier (BBB) via inhibiting the degradation of tight junction proteins (TJPs) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Taken together, these findings indicated that [email protected] may serve as a promising dual-targeting therapeutic agent for alleviating cerebral I/R injury. Statement of Significance Cerium (Ce)-doped Linde Type A zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme were designed for inducing neuroprotection after ischaemic stroke by reducing dysfunction of the neurovascular unit (NVU). [email protected] had the ability to adsorb excessive Zn 2+ and showed mimetic enzymatic activities . As a result, [email protected] protected against cerebral ischaemia and reduced the damage of NVU by improving the integrity of blood brain barrier (BBB) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). These findings indicated that [email protected] may serve as a therapeutic strategy for neuroprotection and functional recovery upon ischaemic stroke onset.
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Small
·
2021
·Vol. 18
·期 6
·2103528
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IF 13.281
Bijiang Geng,Shuang Xu,Ping Li,Xiaokai Li,Fuling Fang,Dengyu Pan,Longxiang Shen
Sonodynamic therapy as a promising noninvasive modality is being developed for tumor therapy, but there is a lack of next-generation sonosensitizers that can generate full ROS at high yields and simultaneously deplete elevated levels of glutathione (GSH) in tumor cells. Semiconductor p-n junctions are engineered as high-efficacy sonosensitizers for sonodynamic tumor eradication using pyridine N-doped carbon dots (N-CDs) as a p -type semiconductor and oxygen-deficient TiO 2− x nanosheets as a n -type semiconductor. The rate constants of 1 O 2 and •OH generation by ultrasound-excited N-CD@TiO 2− x p-n junctions are 4.3 and 4.5 times higher than those of TiO 2 , respectively. A Z-scheme carrier migration mechanism in the p-n junction achieving the rapid spatial separation of the ultrasound-generated electron–hole pairs for enhanced full ROS production is proposed. GSH-cleavable, Pt-crosslinked, N-doped CD fluorescent probes to detect the presence of intracellular GSH are also constructed. A GSH-responsive, p-n junction platform (Pt/N-CD@TiO 2− x ) with integrated GSH detection, GSH depletion, and enhanced sonodynamic performance is then assembled. Malignant tumors are completely eradicated without relapse via intravenous administration of low-dose Pt/N-CD@TiO 2− x under ultrasound irradiation. This work substantiates the great potential of biocompatible, GSH-responsive p-n junctions as next-generation sonosensitizers via p-n junction-enhanced ROS generation and metal ion oxidation of intracellular GSH.
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Acta Biomaterialia
·
2021
·
IF 8.947
Shuocheng Huang,Shibo Xu,Yanan Hu,Xingjun Zhao,Linna Chang,Zhenhua Chen,Xifan Mei
Multidrug-resistant (MDR) bacteria-induced infection is becoming a huge challenge for clinical treatment, especially for non-healing diabetic wound infections, which increase patient mortality. MRSA infections and delayed wound healing (methicillin-resistant Staphylococcus aureus) accounted for a higher proportion. Although surgical debridement and continuous use of antibiotics are still the main clinical treatments, new multifunctional therapeutic nanoplatform are attractive for MIDW. Thus, in the present study, black phosphorus quantum dots (BPQDs) encapsulated in hydrogel ( [email protected] ) were utilized as nanoplatforms for MIDW treatment to achieve the multifunctional properties of NIR (near infrared) responsiveness, ROS (reactive oxygen species) generation and antibacterial activity . Upon NIR irradiation, the temperature of the [email protected] MIDW area rapidly increased up to 55 °C for sterilization. In vitro experiments showed that [email protected] exerted a synergistic effect on inhibiting MRSA by producing of ROS, lipid peroxidation , glutathione , adenosine triphosphate accumulation and bacterial membrane destruction upon NIR irradiation. The resulting [email protected] achieved an effective sterilization rate of approximately 90% for MRSA. Furthermore, animal experiments revealed that [email protected] achieved an effective closure rate of 95% for MIDW after 12 days by reducing the inflammatory response and regulating the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Meanwhile, intravenous circulation experiments showed good biocompatibility of BPQDs, and no obvious damage to rat major organs was observed. The obtained results indicated that [email protected] achieved the synergistic functions of NIR-responsiveness, ROS generation, and antibacterial activity and promoted wound healing, suggesting that they are promising multifunctional nanoplatforms for MIDW healing. Statement of significance 1. NIR-triggered ROS-generating and antibacterial nanoplatforms are attractive in the wound healing field. 2. In this work, black phosphorus quantum dots encapsulated in a hydrogel were used as a nanoplatform for treating MRSA infected wounds. 3. The obtained materials have achieved an effective sterilization rate for MRSA and effective wound closure rate.
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CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Bing Wang,Kai Chen,Qianfeng Zhang,Lei Gu,Qiang Luo,Zhiqian Li,Qiyong Gong,Hu Zhang,Zhongwei Gu,Kui Luo
Reactive oxygen species (ROS)-responsive drug delivery systems for cancer treatment often suffer insufficient drug release. Herein, we developed a ROS-responsive amphiphilic block copolymer-drug conjugate, TA-CA-Prodrug, based on a positive feedback strategy to address this issue. Cinnamaldehyde (CA), a ROS-generation agent, was modified as a ROS-responsive linker in the copolymer to connect hydrophilic and hydrophobic segments and conjugate an anti-tumor drug (PTX) to the main copolymeric chain. A pH-sensitive moiety (DPA) was also incorporated to the copolymer. This amphiphilic prodrug self-assembled into micelles at a particle size of around 150 nm with a negative zeta potential. ROS-responsive release of PTX and CA was confirmed after TA-CA-Prodrug was incubated with H 2 O 2 , and the drug release rate was dependent on the concentration of H 2 O 2 . After endocytosis into tumor cells, TA-CA-Prodrug were mainly colocalized with mitochondria owing to the charge reversal after protonation of DPA moieties of TA-CA-Prodrug in an acidic intracellular environment (i.e., pH ≤ 6.2). A relatively high level of ROS around the mitochondria induced simultaneous release of CA and PTX from the prodrug. Then, ROS-generation was triggered by released CA, which in turn enhanced PTX release and PTX-mediated cell cycle arrest, thus resulting in remarkable apoptosis of tumor cells after treatment with TA-CA-Prodrug compared with control groups (TK-Prodrug and Prodrug). Due to a cascaded ROS-feedback strategy, i.v. injection of TA-CA-Prodrug into mice bearing 4 T1 tumors led to a greater tumor inhibition efficacy than control groups, and no obvious side effects were confirmed from negligible changes in body weight as well as H&E stained major organs of mice. Therefore, this block copolymer-drug conjugate could enhance intracellular ROS production for efficient drug release and augment its anti-tumor effect.
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INFECTION GENETICS AND EVOLUTION
·
2021
·
IF 3.342
Dongmei Jia,Wenping Sun
Objectives A frequent emergence of drug resistance has been observed and posed great threat to global public health recently. This work aimed to investigate the potential synergistic effect and the underlying mechanisms of AgNPs-fluconazole combination more extensively through 2 clinically isolated fluconazole-resistant Candida albicans ( C. albicans ) strains. Methods Antifungal properties of AgNPs and fluconazole alone or together against planktonic cells and biofilms were tested. Cellular and molecular targets associated with fluconazole resistance were monitored after AgNPs treatment. Antifungal potential of AgNPs-fluconazole combination was also explored in vivo using a mouse model of disseminated candidiasis. Tissue burden and survival rate were analyzed. Results The results indicated that AgNPs worked synergistically with fluconazole against both planktonic cells of fluconazole-resistant C. albicans and biofilms formed <12 h. AgNPs treatment down-regulated ERG1 , ERG11 , ERG25 , and CDR2 , decreased membrane ergosterol levels and membrane fluidity, reduced membrane content of Cdr1p, Cdr2p, and thus efflux bump activity. The elevated ROS production was also a likely cause of the synergistic effect. In vivo , AgNPs and fluconazole combination significantly decreased the fungal burden and improved the survival rate of infected mice. Conclusion In conclusion, these results further confirm that AgNPs-fluconazole combination is a hopeful strategy for the treatment of fluconazole-resistant fungal infections.
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BIOCONJUGATE CHEMISTRY
·
2021
·
IF 4.774
Chunxiao Sui,Rui Tan,Yiwen Chen,Guotao Yin,Ziyang Wang,Wengui Xu,Xiaofeng Li
Metal–organic frameworks (MOFs) derivatives had been widely explored in electronic and environmental fields, but rarely evaluated in the biomedical applications. Herein, Fe–N codoped carbon (FeNC) nanoparticles were synthesized and characterized via facile pyrolysis of precursor ZIF-8 (Fe/Zn) nanoparticles, and their potential applications in tumor therapy were assessed in this investigation both in vitro and in vivo. After PAA (sodium polyacrylate) modification, the FeNC@PAA nanoparticles were able to initiate a Fe-based Fenton-like reaction to generate ·OH and O2 for chemodynamic therapy (CDT) and O2 evolution. Meanwhile, the porphyrin-like metal center in the FeNC@PAA nanoparticles could be used as a photosensitizer for photodynamic therapy (PDT) of tumors, which could be enhanced by O2 generated in CDT. Furthermore, the FeNC@PAA nanoparticles were also found to be effective in photothermal therapy (PTT) with a photothermal conversion efficiency of 29.15%, owing to a high absorbance in the near-infrared region (NIR). In conclusion, the synthesized FeNC@PAA nanoparticles exhibited promising applications in O2 evolution and CDT/PDT/PTT synergistic treatment of tumors.
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