ACS Applied Bio Materials
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2026
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IF 4.7
Aolei Hu,Xilu Chen,Haimei Ling,Zhenzi Mi,Ruilian Yu,Yao Fu
Malignant melanoma has a high recurrence rate after surgical resection, conventional neoadjuvant chemotherapy (NAC) suffers from off-target toxicity and limited efficacy. Leveraging elevated tumor-specific reactive oxygen species (ROS), we designed a sequential therapeutic strategy combining ROS-responsive micelles and a multifunctional hydrogel to combat local recurrence. By conjugating 3-indoleacetic acid to chondroitin sulfate via a ROS-responsive thioketal linker, an amphiphile (CS-TK-IAA, CTI) was synthesized, significantly enhancing tumor-specific uptake and ROS-scavenging capacity. CTI self-assembled into micelles (CLT@CTI) encapsulating celastrol (CLT), achieving high encapsulation efficiency (92.3%) and drug loading capacity (25.2%). Postoperatively, an injectable chitosan-based hybrid hydrogel (CPG) with self-healing, tissue adhesion, and hemostatic properties was applied to the resection site, triggering a photothermal effect via near-infrared light. In a mouse melanoma recurrence model, neoadjuvant CLT@CTI therapy effectively suppressed primary tumor growth, while postoperative CPG gel-mediated photothermal ablation of residual tumors dramatically delayed recurrence and improved 60-day survival rates. This sequential therapeutic regimen, neoadjuvant chemotherapy with postoperative photothermal therapy, provides a promising and viable solution for preventing melanoma recurrence.
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Materials Today Bio
·
2026
·
IF 11
Xiaoqing Zhou,Guangyun Hu,Can Huang,Ying Liu,Zhou-rui Ma,Yuangang Lu,Yong Xu,Wei Qian
Intractable wounds remain a major clinical challenge due to persistent oxidative stress, dysregulated inflammation, and impaired macrophage polarization. Here, we develop a therapeutic cryogel by integrating ultrasmall Prussian blue (USPB) nanozymes into a GelMA–quaternary ammonium chitosan methacryloyl matrix via cryogelation. The resulting Cryogel@USPB features high porosity, large interconnected pores, and strong swelling capacity, supporting its application in wound environments. Cryogel@USPB exhibits potent catalase-, peroxidase-, and superoxide dismutase-like activities, enabling efficient ROS scavenging. In vitro, it promotes macrophage polarization toward a regenerative phenotype and suppresses pro-inflammatory cytokines. In vivo, Cryogel@USPB significantly accelerates healing in deep second-degree burn and diabetic wound models, achieving wound closure rates of 94.07 ± 1.94% and 98.69 ± 1.02%, respectively, with improved skin structure and collagen deposition. Mechanistically, Cryogel@USPB modulates the wound microenvironment by inhibiting cGAS–STING signaling. These findings identify Cryogel@USPB as a promising immuno-regulatory nanozyme platform for treating complex wounds.
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Biomaterials Advances
·
2026
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IF 6.7
Ming Zhu,Shimin Dai,Jingquan Cui,Zhibo Zhao,Xingchen Wei,Ping Li,Wei Li
ROS-responsive hydrogel delivers CircSERPINE2-engineered exosomes. • Boronate ester cleavage scavenges ROS for controlled exosome release. • BV@cSERPINE2-Exo promotes M2 macrophage polarization and chondrogenesis. • Intra-articular injection yields near-complete hyaline cartilage repair. Osteoarthritis (OA) involves chronic inflammation and oxidative stress, both of which impair cartilage regeneration. To counteract these pathological processes, bone marrow mesenchymal stromal cell (BMSC)-derived exosomes have emerged as a promising therapy. These exosomes promote chondrogenesis and facilitate chemokine-guided cell homing. However, hostile microenvironments compromise their efficacy. This study developed a cell-free, ROS-responsive boronate-vinyl (BV) hydrogel platform encapsulating BMSC-derived exosomes overexpressing CircSERPINE2 (BV@cSERPINE2-Exo), which were isolated via ultracentrifugation from lentivirus-transduced BMSCs. This platform enables sustained microenvironmental modulation and functional cartilage regeneration. The hydrogel forms through dynamic boronate ester crosslinking between phenylboronic acid-modified poly γ-glutamic acid and polyvinyl alcohol (PVA). It exhibits rapid gelation, shear-thinning injectability, and potent ROS-scavenging capacity. ROS-triggered cleavage of the boronate ester bonds ensures controlled exosome release. In vitro, BV@cSERPINE2-Exo shifted LPS-stimulated macrophages from an M1 to M2 phenotype by decreasing iNOS and IL-1β levels and increasing Arg-1 and IL-10. Concurrently, the system protected chondrocytes from TNF-α-induced degeneration by downregulating MMP13 and restoring COL2A1, SOX9, and proteoglycan synthesis. In a rat patellar cartilage defect model, intra-articular injection of BV@cSERPINE2-Exo promoted deposition of cartilage-specific extracellular matrix and achieved near-complete hyaline cartilage-like repair within 8 weeks. This repair was superior to that in the BV hydrogel or unmodified exosome control groups. These results establish a smart, injectable biomaterial strategy that integrates precise ROS-responsive circRNA delivery with immunomodulation, offering a promising early intervention strategy for cartilage defect repair and the prevention of osteoarthritis progression.
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Materials Today Bio
·
2026
·
IF 11
Yu He,Xiaoqi Yang,Yongke Bai,Xiaozhuo Ba,Tao Ye,Zichen Zhong,Zhiqiang Chen,Heng Li,Kun Tang
Calcium oxalate (CaOx) nephrocalcinosis is a chronic kidney disease marked by CaOx crystal deposition, oxidative stress, neutrophil infiltration, and renal tubular epithelial cell injury. To date, no targeted therapies are clinically available for this condition. Antioxidant nanomaterials capable of scavenging excessive reactive oxygen species (ROS) offer a promising approach for treating CaOx crystal-induced kidney injury. Neutrophil-mediated delivery systems have been leveraged to transport nanomaterials to inflamed kidneys for acute kidney injury therapy, and their targeting specificity can be further augmented through the functionalization of cell membranes with targeting peptides. Herein, we developed a biomimetic nanoplatform by loading DNase I onto black phosphorus nanosheets (BPNSs) and coating them with a neutrophil membrane modified with a CD44-targeting peptide (PNM@D@BP), aiming to ameliorate renal CaOx crystal deposition and the consequent kidney injury. The engineered neutrophil membrane coating conferred the nanocarrier with the ability to home to sites of renal injury and inflammation. PNM@D@BP exhibited potent antioxidative activity, effectively eliminating CaOx crystal-induced ROS. In both in vivo and in vitro settings, PNM@D@BP was shown to suppress the formation of neutrophil extracellular traps (NETs). Moreover, RNA sequencing and bioinformatic analyses revealed that PNM@D@BP protects against CaOx crystal-induced kidney injury by modulating oxidative stress and neutrophil-driven inflammatory responses. Collectively, these findings underscore the therapeutic potential of PNM@D@BP for the treatment of CaOx kidney stones.
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Acta Pharmaceutica Sinica B
·
2026
·
IF 14.6
Huanxin Lin,Yao Liu,Zifang Liu,Yong Luo,Conghan Wang,Yaqing Ding,Zeqian Huang,Chunshun Zhao
Metastasis remains the principal driver of breast cancer mortality, a complex process shaped by two key hallmarks: an immunosuppressive tumor microenvironment that facilitates pre-metastatic niche formation and the persistent activation of the pro-metastatic CXCL12–CXCR4 chemokine axis. To simultaneously blockade these drivers, we developed a multifunctional, H 2 O 2 -responsive nanoplatform composed of self-assembled HA-AMD-Cu and the prodrug CBD. This innovative system leverages competitive coordination chemistry to achieve the precise in situ generation of therapeutics specifically within the tumor site. Under the elevated H 2 O 2 levels characteristic of the tumor microenvironment, CBD releases diethyldithiocarbamate (DTC), which effectively competes for Cu 2+ from the HA-AMD-Cu complex. This reaction generates cytotoxic Cu(DTC) 2 while liberating the active multivalent CXCR4 antagonist, HA-AMD. Consequently, Cu(DTC) 2 exerts potent tumor-selective cytotoxicity and induces robust immunogenic cell death (ICD) to reactivate suppressed anti-tumor immunity, while HA-AMD simultaneously inhibits CXCL12-driven metastatic spread. This precise “off-to-on” switch demonstrated significant therapeutic efficacy against both primary tumors and lung metastases in aggressive breast cancer models. Collectively, integrating multivalent CXCR4 blockade with tumor-selective ICD induction provides a promising, targeted strategy for combating metastatic breast cancer.
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Materials Today Bio
·
2026
·
IF 11
Zhaohua Yang,Shutian Zhang,Wenrui Ma,Hongqiang Zhang,Shouguo Yang,Xiaoning Sun,Mengni Zhu,Chunsheng Wang,Yixuan Wang
Heart transplantation offers the only life-saving option for patients with terminal heart failure; yet, the sequential "innate-adaptive" avalanche initiated by ischemia-reperfusion injury (IRI) remains the Achilles' heel of long-term graft acceptance. Current regimens overwhelmingly focus on either the adaptive or the IRI-triggered innate arm, failing to interrupt the positive-feedback loop that amplifies allo-rejection. To address this unmet need, we herein present a single ROS-responsive nanoplatform that weds dual immunosuppression with on-demand oxygenation Fe 3 O 4 @CaO 2 @Tac@HA. The core-shell Fe 3 O 4 @CaO 2 carrier simultaneously loads hyaluronic acid (HA), which is a potent dampener of innate inflammatory signaling, and tacrolimus (Tac), which is a calcineurin inhibitor that arrests adaptive T-cell activation. Upon exposure to the ROS-rich milieu of the reperfused graft, CaO 2 undergoes conversion to O 2 , promptly relieving tissue hypoxia while reducing oxidative stress. In vitro , the nanocomposite exhibits rapid ROS scavenging, sustained oxygen release and inhibit T cell activation; in vivo, it markedly prolongs cardiac-allograft survival by synchronously suppressing innate immune cells infiltration and CD8 + T-cell cytotoxicity. Collectively, Fe 3 O 4 @CaO 2 @Tac@HA offers a translatable "one-two punch" strategy that unites innate and adaptive immunomodulation, setting the stage for precision nanotherapy in cardiac transplantation.
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BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Baiyi Yan,Yanchun Gong,Wei Meng,Huizhen Sun,Wenxi Li,Kaizhi Ding,Caixia Dang,Xiaofei Gao,Wei Sun,Chunhua Yuan,Songhua Wang,Li-Hua Yao
Type 2 diabetes mellitus (T2DM) is a common and multiple endocrine metabolic disease. When pancreatic β cell in case of dysfunction, the synthesis and secretion of insulin are reduced. This study is to explore the effect of cordycepin (the molecular formula C 10 H 13 N 5 O 3 ), a natural adenosine isolated from Cordyceps militaris , on high glucose/lipid-induced glucotoxicity and lipotoxicity in INS-1 cells. Our results showed that cordycepin improved cell viability, improved cell energy metabolism and promoted insulin synthesis and secretion. The mechanism may be related to that cordycepin reduces intracellular reactive oxygen species (ROS), increases ATP content in cells, causes membrane depolarization and balances the steady state of Ca 2+ concentration, cordycepin inhibits cell apoptosis, which may be related to the downregulation of proteins level of c-Jun N-terminal kinases (JNK) phosphorylation, cytochrome c (Cyt-c), Cleaved Capase-3, the mRNA level of JNK, Cyt-c, Capase-3 and upregulation of proteins/mRNA level of pancreatic and duodenal homeobox factor-1 (PDX-1). These results suggest that cordycepin can inhibit cell apoptosis and protect cell number by downregulating ROS/JNK mitochondrial apoptosis pathway under high glucose/lipid environment, thereby improving the function of pancreatic islet cells, providing a theoretical basis for the related research on the prevention and control of cordycepin on T2DM.
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CARBOHYDRATE POLYMERS
·
2023
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IF 11.2
Xiaomei Dai,Xiaojun Liu,Yu Li,Qingqing Xu,Lele Yang,Feng Gao
Staphylococcus aureus ( S. aureus ) residing in host macrophages is hard to clear because intracellular S. aureus has evolved mechanisms to hijack and subvert the immune response to favor intracellular infection. To overcome this challenge, nitrogen-phosphorous co-doped carbonized chitosan nanoparticles (NPCNs), which possess the polymer/carbon hybrid structures, were fabricated to clear intracellular S. aureus infection through chemotherapy and immunotherapy. Multi-heteroatom NPCNs were fabricated through the hydrothermal method , where chitosan and imidazole were used as the C and N sources and phosphoric acid as the P source. NPCNs can not only be used as a fluorescent probe for bacteria imaging but also kill extracellular and intracellular bacteria with low cytotoxicity. NPCNs could generate ROS and polarize macrophages into classically activated (M1) phenotypes to increase antibacterial immunity. Furthermore, NPCNs could accelerate intracellular S. aureus -infected wound healing in vivo. We envision that these carbonized chitosan nanoparticles may provide a new platform for clearing intracellular bacterial infection through chemotherapy and ROS-mediated immunotherapy.
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CARBON
·
2022
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IF 11.307
Honghai Song,Yinwen Ji,Yutao Zhu,Jiechao Xia,Chuan Hu,Yang Jin,Jin Zhang,Zhijun Hu,Jiayong Dai
Reactive oxygen species (ROS) played an essential role in regulating various physiological functions in living organisms and treatment of malignant disease. Herein, a new type of PEGylated carbon nitride [email protected] polyaniline ( [email protected] ) with nano-heterostructure and dual-modal catalytic ROS generation performance was synthesized. Formation of the nano-heterostructure promoted separation of photo-induced electron-hole pairs, and doping of Cu 2+ further increased electron-transfer rate greatly. Besides, antenna effect of the CuPANI endowed the heterostructure with near-infrared light utilization ability, finally inducing concurrences of oxygen-independent type I and oxygen-dependent type II photodynamic therapy simultaneously. Interestingly, unleashing of doped Cu 2+ ions responded to reductive glutathione in tumor microenvironment further triggered a Fenton-like reaction, and such PEGylated [email protected] with remarkable ROS generation ability was therefore employed for high-metastatic orthotopic osteosarcoma therapy. Cell proteomics analysis illustrated that cell survival and adhesion were considerably altered by the massively-generated ROS, which also affected efficiencies of conspicuous orthotopic tumor therapy and pulmonary metastasis resistance in vivo . To summarize, our newly-proposed PEGylated [email protected] achieved desirable effects on killing orthotopic osteosarcoma and preventing metastasis, providing a new therapeutic strategy for malignant tumor treatment.
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Biomaterials Science
·
2023
·Vol. 11
·期 6
·2243-2252
·
IF 6.6
Anni Cui,Ying Bao,Haitao Xu,Xin Mu,Xiahua Zhong,Wynn Wee,Fanqi Wu,Guiye Shan
The rapid emergence of drug-resistant bacteria has attracted great attention to exploring advanced antibacterial methods. However, single-modal antibacterial therapy cannot easily eliminate drug-resistant bacteria completely due to its low efficacy. Therefore, it is essential to achieve multi-modal antibacterial therapy effectively. Herein, a dual-modal ROS generator was designed based on photosensitive PDA–MnO2@Ce6/liposome (PMCL) nanozymes for synergistic chemo-photodynamic therapy. PMCL nanozymes adhere to bacteria through liposome–membrane fusion. Meanwhile, PMCL catalyzes endogenous hydrogen peroxide (H2O2) to generate hydroxyl radicals (˙OH) and singlet oxygen (1O2) under laser irradiation. Furthermore, the photothermal effect can accelerate the generation of ROS. Based on dual-enzyme activities (mimicking peroxidase and catalase) and photodynamic properties, PMCL achieves powerful antibacterial efficacy and mature bacterial biofilm eradication. With the synergistic chemo-photodynamic effects, bacterial populations decrease by >99.76% against Gram-positive S. aureus and Gram-negative E. coli. Notably, the synergistic antibacterial properties of PMCL nanozymes are further explored using a mouse wound model of S. aureus infection. This work fabricated an efficient dual-modal ROS generator to kill bacteria, further providing a new strategy for treating wound infection.
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Frontiers in Oncology
·
2023
·
IF 4.7
Hao Yin,Xingyan Fu,Hanyu Gao,Han Gao,Yannan Ma,Xitong Chen,Xueqi Zhang,Shan-Shan Du,Yun-Kun Qi
Liver cancer is the third leading cause of cancer-associated mortality globally, and >830,000 patients with liver cancer undergoing treatment succumbed to the disease in 2020, which indicates the urgent need to develop a more effective anti-liver cancer drug. In our previous study, nucleus-targeting hybrid peptides obtained from the fusion of LTX-315 and the rhodamine B group possessed potent anti-adherent cancer cell activity. Hybrid peptides accumulated in the cell nucleus and damaged the nuclear membrane, resulting in the transfer of reactive oxygen species (ROS) from the cytoplasm to the nucleus and the induction of apoptosis. However, the source of the high concentration of ROS within the cytoplasm is unclear. Moreover, although our previous study demonstrated that hybrid peptides possessed potent anticancer activity against adherent cancer cells, their efficacy on liver cancer remained unexplored. The current study found that the hybrid peptide NTP-217 killed liver cancer cells after 4-h treatment with a half-maximal inhibitory concentration of 14.6-45.7 μM. NTP-217 could stably accumulate in the liver tumor tissue and markedly inhibited liver tumor growth in mice. Furthermore, NTP-217 destroyed mitochondria and induced the leakage of mitochondrial contents, resulting in the generation of a substantial quantity of ROS. Unlike the apoptosis induced by 24 h of treatment by NTP-217, 4 h of treatment caused ROS-mediated necrotic cell death. These findings suggested that short-time treatment with hybrid peptides could trigger ROS-mediated rapid necrosis in liver cancer cells, and provided a basis for the future development of hybrid peptides as anti-liver cancer agents.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Xiaofei Wang,Hongxiu Wei,Yangcen Ou,Zhen Li,Feng Luo,Hong Tan,Jiehua Li
Development of an inflammation modulating polypropylene (PP) mesh in pelvic floor repair is an urgent clinical need. This is because PP mesh for pelvic floor repair can cause a series of complications related to foreign body reactions (FBR) in postoperative period. Therefore, we successfully prepared PP composite mesh that can scavenge reactive oxygen species (ROS) and inhibit inflammation to moderate FBR by a simple method. First, a pregel layer was formed on PP mesh by dip coating. Among them, polyurethane with polythioketal (PTK) is an excellent ROS scavenger, and dopamine methacrylamide (DMA) improves the stability of the coating and synergistically scavenges ROS. Then, a composite mesh (optimal PU50-PP) was obtained by photopolymerization. The results showed that the polyurethane gel layer was able to scavenge more than 90% of free radicals and about 75% of intracellular ROS. In vitro , PU50-PP mesh significantly scavenged ROS and resisted macrophage adhesion. After implantation in the posterior vaginal wall of rats, PU50-PP eliminated 53% of ROS, inhibited inflammation (decreased IL-6, increased IL-10), and dramatically reduced collagen deposition by about 64%, compared to PP mesh. Thus, the composite PP mesh with ROS scavenging and anti-inflammatory properties provides a promising approach for mitigating FBR.
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