INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Donghui Zhao,Yunhao Deng,Junyi Shi,Xinye Ni,Chaoqing Li,Yang Bai,Yang Xuan,Jianhao Wang
Nanozymes with multienzyme activity for reactive oxygen species (ROS) generation and intracellular redox imbalance are attractive strategy for cancer therapy. However, it is severely limited by low biocompatibility and catalytic efficiency, hypoxic and high levels of GSH in the tumor microenvironment. To address these issues, a copper doping carbon nanozyme (CC) with multienzyme activity was designed and integrated with photosensitizer Ce6 and gelatin to fabricate ROS amplifier (CCC). Gelatin endowed CCC with good biocompatibility, low hemolysis, and enzyme responsive degradation. CCC with high CAT-like, POD-like, OXD-like, and GSHox-like activities can induce the intracellular ROS storm formation to eliminate the cancer cells. The OXD-like activity and PDT performance mediated 1 O 2 generation was markedly potentiated by the CAT-like activity of CCC via catalyzing high expression of H 2 O 2 to generate O 2 . At the same time, a large amount of ·OH were produced through POD-like activity of CCC and GSH was depleted by the GSHox-like activities of CCC, resulting in a destructive ROS storm formation and cellular redox homeostasis disruption. Both in vivo and in vitro experiments showed that CCC displayed satisfactory anti-tumor activity and biocompatibility. Our work provides a novel strategy for the development of nanozyne enhanced photodynamic therapy of cancer.
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ACS Applied Materials & Interfaces
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2025
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IF 8.2
Miaomiao Yao,Qi He,Yameng Tao,Xiaoyang Kang,Xinru Wu,Fangkai Shi,Yujia Wei,Jingjing Liu,Zhiyun Meng,Ruolan Gu,Hui Gan,Guifang Dou,Shuchen Liu,Yunbo Sun
Blue fluorescent carbon quantum dots (CDs) were synthesized by a one-step hydrothermal method using chitosan as the only raw material. This material overcomes multifunctional integration limitations in traditional dressings, achieving coordinated wound repair across all phases. During inflammation (0–3 days), CDs scavenge reactive oxygen species and suppress inflammatory factors (TNF-α↓49.63%, IL-6↓70.8%). In proliferation (3–7 days), they promote angiogenesis (CD31↑56.89%) and cell proliferation (Ki67↑74.3%). During remodeling (7–14 days), functional parallel collagen deposition occurs (collagen deposition 1.26× Celox group). The seamless “anti-inflammation/prohealing/remodeling” mechanism yielded 59% wound closure by day 3 postirradiation (vs Celox 37.34%). CDs synergistically activate Nrf2 while inhibiting NF-κB pathways, enabling combined anti-inflammatory/antioxidant regulation in irradiated environments. Nanoscale reconstruction retains chitosan’s hemostasis and avoids gene modification/vector loading via one-step synthesis (cost-reduced), with biosafety confirmed by acute toxicity tests. This study provides a prohealing nanomaterial and establishes a paradigm for traditional biomaterial redevelopment.
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FASEB JOURNAL
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2025
·Vol. 39
·期 3
·e70379
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IF 4.2
Jiancheng Yang,Qinghua Tang,Siyu Li,Lei Yang,Ming Yang,Qingmei Li,Yan Feng,Mingming Pan,Yuhong Zeng
The accumulation of intracellular reactive oxygen species (ROS) is widely recognized to stimulate the development of osteoclasts, a crucial factor in the onset of osteoporosis. The ROS scavenging capability of Prussian blue nanoparticles (PBNPs) is exceptional, and they possess excellent biocompatibility. However, the effects of PBNPs on osteoporosis remain unknown. Present study aimed to investigate whether PBNPs could inhibit osteoclast differentiation and prevent ovariectomy (OVX)-induced bone loss by suppressing ROS. In vitro experiments demonstrated that PBNPs attenuated osteoclastogenesis and downregulated the expression of osteoclast-related genes. Mechanistically, PBNPs reduce cellular ROS by blocking RANKL-induced ROS generation and increasing the expression of ROS scavenging enzymes, which in turn block the NF-κB, ERK, JNK, and p38 pathways, thereby reducing NFATc1 signaling. According to in vivo experimental results, OVX caused a significant rise in ROS in the bone marrow, an increase in osteoclastic number on the bone surface, and substantial bone loss; however, PBNPs significantly reduced ROS and successfully protected OVX-induced bone damages. In conclusion, this study showed for the first time that PBNPs prevented OVX-induced bone loss and attenuate osteoclastogenesis, indicating that PBNPs may be a viable alternative therapy for the management of osteoclast-associated bone disorders. Graphical Once RANKL binds to RANK on the cell membrane of BMMs, the NF-κB and MAPK pathways become activated, resulting in the amplification of NFATc1, which upregulates the expression of osteoclast-specific genes such as CTSK , Integrin αV , Atp6v0d2 , and MMP9 . These signaling events are mediated by the RANKL-induced ROS signaling. PBNPs decreased levels of ROS and mitigated these signaling pathways by decreasing ROS production and enhancing the expression of antioxidant enzymes. Consequently, PBNPs prevented osteoclastogenesis.
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Advanced Healthcare Materials
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2024
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IF 10
Wenting Xu,Hongmei Zhou,Bangli Hu,Xinqiang Liang,Yanping Tang,Shufang Ning,He Ding,Piaoping Yang,Chen Wang
Calcium overload can lead to tumor cell death. However, because of the powerful calcium channel excretory system within tumor cells, simplistic calcium overloads do not allow for an effective antitumor therapy. Hence, the nanoparticles are created with polyethylene glycol (PEG) donor-modified calcium phosphate (CaP)-coated, manganese-doped hollow mesopores Prussian blue (MMPB) encapsulating glucose oxidase (GOx), called GOx@MMPB@CaP-PEG (GMCP). GMCP with a three-mode enhancement of intratumor reactive oxygen species (ROS) levels is designed to increase the efficiency of the intracellular calcium overload in tumor cells to enhance its anticancer efficacy. The released exogenous Ca 2+ and the production of cytotoxic ROS resulting from the perfect circulation of the three-mode ROS outbreak generation that Fenton/Fenton-like reaction and consumption of glutathione from Fe 2+ /Fe 3+ and Mn 2+ /Mn 3+ circle, and amelioration of hypoxia from MMPB-guided and GOx-mediated starvation therapy. Photothermal efficacy-induced heat generation owing to MMPB accelerates the above reactions. Furthermore, abundant ROS contribute to damage to mitochondria, and the calcium channels of efflux Ca 2+ are inhibited, resulting in a calcium overload. Calcium overload further increases ROS levels and promotes apoptosis of tumor cells to achieve excellent therapy.
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ACS Biomaterials Science & Engineering
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2024
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IF 5.4
Beibei Zhang,Hao Liu,Yifei Wang,Yong Zhang
Ferroptosis is an appealing cancer therapy strategy based on the H2O2-involved Fenton reaction to produce toxic •OH for lipid peroxidation. However, intracellular H2O2 is easily consumed and results in a deficient Fenton reaction. This obstacle can be overcome by traditional chemotherapeutic drugs for H2O2 supplements. Moreover, a recent work illustrated that dihydroartemisinin (DHA) could promote ferroptosis against tumoral cells, particularly in the presence of ferrous compounds. To achieve combined chemotherapy and ferroptosis, a nanocarrier (TKNPDHA-Fc) was constructed by using thioketal (TK)-bridged paclitaxel prodrug (PEG-TK-PTX) and ferrocene (Fc)-conjugated PEG-Fc, where DHA was encapsulated by a hydrophobic–hydrophobic interaction. Upon cellular uptake, TKNPDHA-Fc could facilitate PTX release through TK breakage under an excess H2O2 microenvironment. Owing to the loss of the hydrophobic PTX component, TKNPDHA-Fc underwent a rapid dissociation for improving DHA to act as a ferroptotic inducer along with Fe supplied from Fc. Moreover, both the chemotherapy-induced reactive oxygen species and the •OH produced from reinforced ferroptosis further stimulated the TK cleavage. The “self-catalytic” loop of TKNPDHA-Fc remarkably improved the antitumor performance in vivo via combined mechanisms, and its tumor inhibition rate reached 78.3%. This work highlights the contribution of ROS-responsive and self-catalytic nanoplatforms for enhancing the potential of combined chemotherapy and ferroptosis for cancer therapy in the future.
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Bioactive Materials
·
2024
·
IF 18
Xiaoxiao Hu,Mo Zhang,Cuilu Quan,Saisai Ren,Wei Chen,Jing Wang
Immunogenic cell death (ICD) represents a modality of apoptosis distinguished by the emanation of an array of damage-related molecular signals. This mechanism introduces a novel concept in the field of contemporary tumor immunotherapy. The inception of reactive oxygen species (ROS) within tumor cells stands as the essential prerequisite and foundation for ICD induction. The formulation of highly efficacious photodynamic therapy (PDT) nanomedicines for the successful induction of ICD is an area of significant scientific inquiry. In this work, we devised a ROS-responsive and triple-synergistic mitochondria-targeted polymer micelle (CAT/CPT-TPP/PEG-Ce6, CTC) that operates with multistage amplification of ROS to achieve the potent induction of ICD. Utilizing an “all-in-one” strategy, we direct both the PDT and chemotherapeutic units to the mitochondria. Concurrently, a multistage cyclical amplification that caused by triple synergy strategy stimulates continuous, stable, and adequate ROS generation (domino effect) within the mitochondria of cells. Conclusively, influenced by ROS, tumor cell-induced ICD is effectively activated, remodeling immunogenicity, and enhancing the therapeutic impact of PDT when synergized with chemotherapy. Empirical evidence from in vitro study substantiates that CTC micelles can efficiently provoke ICD, catalyzing CRT translocation, the liberation of HMGB1 and ATP. Furthermore, animal trials corroborate that polymer micelles, following tail vein injection, can induce ICD, accumulate effectively within tumor tissues, and markedly inhibit tumor growth subsequent to laser irradiation. Finally, transcriptome analysis was carried out to evaluate the changes in tumor genome induced by CTC micelles. This work demonstrates a novel strategy to improve combination immunotherapy using nanotechnology.
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CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Weiwei Zheng,Kefei Zhao,Liang Song,Zhefeng Qian,Wenxing Liu,Yang Zhu,Zhengwei Mao,Changyou Gao
The glial scar forms a disadvantageous microenvironment for neurogenesis after stroke. Single treatment targeting glial scar suppression or neurogenesis promotion is insufficient for stroke repair. To improve the functional recovery post stroke, a synergistical therapy of reactive oxygen species (ROS)-scavenging polymers (hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol, HBPAK) and chondroitin sulfate proteoglycans (CSPGs) receptor (protein tyrosine phosphatase σ, PTPσ) modulatory peptides (intracellular sigma peptide, ISP) was applied in a form of microgels for inflammation alleviation, glial scar inhibition and endogenous neuroblasts regulation. The microgels were prepared with a microfluidic device under UV irradiation. The microgels containing HBAPK displayed efficient elimination of typical ROS of 1-diphenyl-2-picryl hydrazyl radical (DPPH) and H 2 O 2 . The microgels containing HBAPK and ISP peptides decreased inflammation response of lipopolysaccharide (LPS) activated BV2 microglia. Promoted cell migration and proliferation of Schwann cells (SCs) and strengthened cell stemness and neuronal differentiation of neural stem cells (NSCs) were shown when these cells were incubated within the microgels containing HBAPK and ISP peptides. Injection of the microgels in vivo achieved positive therapeutic effects with respect to motor dysfunction recovery promotion, inflammation alleviation and cell apoptosis reduction at 7 d, and astrocytic scar inhibition, neuroblasts promotion and axonal neurofilaments increase at 28 d post stroke, suggesting the effectiveness of this synergistical therapy for stroke.
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ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Yanling Wang,Lishi Luo,Tuotuo Zhang,Jun-Rui Hu,Huiling Wang,Feng Bao,Chonglu Li,Yao Sun,Junrong Li
Sonodynamic therapy (SDT) can generate reactive oxygen species (ROS) to combat multidrug-resistant biofilms, which pose significant challenges to human health. As the key to producing ROS in SDT, the design of sonosensitizers with optimal molecular structures for sufficient ROS generation and activity in complex biofilm matrix is essential. In this study, we propose a π-expansion strategy and synthesize a series of small-molecule metal Ru(II) complexes (Ru1–Ru4) as sonosensitizers (Ru1–Ru4) to enhance the efficacy of SDT. Among these complexes, Ru4 demonstrates remarkable ROS generation capability (∼65.5-fold) that surpasses most commercial sonosensitizers (1.3- to 6.7-fold). Through catalyzing endogenous H2O2 decomposition, Ru4 facilitates the production of abundant O2 as a resource for 1O2 and the generation of new ROS (i.e., •OH) for improving SDT. Furthermore, Ru4 maintains the sustained ROS activity via consuming the interferences (e.g., glutathione) that react with ROS. Due to these unique advantages, Ru4 exhibits potent biofilm eradication ability against methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo, underscoring its potential use in clinical settings. This work introduces a new approach for designing effective sonosensitizers to eliminate biofilm infections, addressing a critical need in healthcare management.
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2024
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IF 4.4
Kangyuan Hu,Xiuhua Li,Zhaodan Tan,Yan Shi
Ovarian cancer is the most common malignant tumor in women. Shikonin (SHK), an herbal extract from Chinese medicine, shows promise in treating ovarian cancer by inducing reactive oxygen species (ROS). However, its clinical use is limited by poor tumor targeting and low bioavailability, and its therapeutic potential is further compromised by the elevated levels of antioxidants such as glutathione (GSH) within tumor cells. In this study, a novel formulation of ROS-responsive micelles loaded with SHK was developed using hyaluronic acid-phenylboronic acid pinacol ester conjugation (HA-PBAP) for targeted therapy of ovarian cancer through disruption of intracellular redox homeostasis. The SHK@HA-PBAP exhibits targeted delivery to ovarian cancer cells through the interaction between HA and CD44 receptors. Upon internalization by cancer cells, the high levels of intracellular ROS triggered the degradation of SHK@HA-PBAP and simultaneously released SHK and generated GSH scavenger quinone methide (QM). The SHK and QM released from the SHK@HA-PBAP effectively induce the production of ROS and deplete intracellular GSH, leading to the disruption of intracellular redox homeostasis and subsequent induction of cell death. These characteristics collectively inhibit the growth of ovarian cancer. In vitro and in vivo studies have demonstrated that SHK@HA-PBAP micelles exhibit superior antitumor efficacy compared to free SHK in both A2780 cells and A2780 tumor-bearing mice. The ROS-responsive SHK@HA-PBA presents a promising therapeutic approach for the treatment of ovarian cancer.
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Nano Research
·
2024
·
IF 9.5
Li Xinyang,Ding Binbin,Li Jing,Han Di,Chen Hao,Tan Jia,Meng Qi,Zheng Pan,Ma Ping’an,Lin Jun
Chemodynamic therapy (CDT), an inventive approach to cancer treatment, exploits innate chemical processes to trigger cell death through the generation of reactive oxygen species (ROS). While offering advantages over conventional treatments, the optimization of CDT efficacy presents challenges stemming from suboptimal catalytic efficiency and the counteractive ROS scavenging effect of intracellular glutathione (GSH). In this study, we aim to address this dual challenge by delving into the role of copper valence states in CDT. Leveraging the unique attributes of copper-based nanoparticles, especially zero-valent copper nanoparticles (CuPd NPs), we aim to enhance the therapeutic potential of CDT. Our experiments reveal that zero-valent CuPd NPs outperform divalent copper nanoparticles (Ox-CuPd NPs) by displaying superior catalytic performance and sustaining ROS generation through a dual approach integrating peroxidase-like (POD-like) activity and Cu + release. Notably, zero-valent NPs exhibit enhanced GSH depletion compared to their divalent counterparts, thereby intensifying CDT and inducing ferroptosis, ultimately resulting in high-efficiency tumor growth inhibition. These findings reveal the impact of valences on CDT, providing novel insights for the optimization and design of CDT agents.
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CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Min You,Yaxin Guo,Hui Yu,Haiyan Yin,Xinlei Shi,Ziqing Tang,Jia Yang,Gang Qin,Jianliang Shen,Qiang Chen
Diabetic wound healing is severely affected by the vicious cycle of wound exposure and impaired repair ability. Here, a polyphenol-enhanced wet adhesion hydrogel with the synergistic effect of mechanical activation and reactive oxygen species (ROS) scavenging was developed to promote the healing of infected diabetic wounds. The hydrogel was copolymerized with acrylic acid (AAc), 1-vinylimidazole (VI), and tannic acid (TA) in dimethyl sulfoxide, followed by solvent exchange with water to obtain a strong toughness and wet adhesion hydrogel (PAAcVI-TA hydrogel). The introduction of TA not only enhanced the toughness and wet tissue adhesive strength of the PAAcVI-TA hydrogel but also conferred outstanding ROS scavenging performance, inflammatory inhibition, and vascular growth promotion. More importantly, the PAAcVI-TA hydrogel could transmit mechanical control force to wet skin through robust adhesion and mechanically contract diabetic wounds. After stretching, the tough PAAcVI-TA hydrogel presented excellent resilience, which allowed for long-term contraction of the diabetic wound, reduced bacterial infection, promoted granulation tissue formation and collagen deposition, and accelerated re-epithelialization. As a result, the PAAcVI-TA hydrogel, which combined mechanical activation with ROS scavenging, might provide a new approach to the effective treatment of diabetic wounds and other forms of chronic wounds.
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BIOMATERIALS
·
2025
·
IF 12.9
Silin Du,Guangyu Ma,Xiang Li,Minghao Chao,Liying Fan,Zhiqiang Zhao,Rongze Tang,Junjie Li,Chaonan Jing,Yufan Liu,Dehong Yu,Zhao Liu,Fenglei Gao
To overcome the resistance of tumor cells to death through a single pathway, PANoptosis, a novel synergistic mode of cell death, can simultaneously activates pyroptosis, apoptosis, and necroptosis. Most current strategies for inducing PANoptosis focused on amplifying reactive oxygen species (ROS) through exogenous stimuli, while the regulatory role of tumor cell metabolic characteristic in this process has long been overlooked. We propose a ROS-Metabolism dual axis synergistic induction of PANoptosis, simultaneously enhancing antitumor immune responses, and construct a novel bionic nanoplatform named CVOVM. This platform consists of CoVO x nanocakes and the glutamine transporter inhibitor V-9302, with 4T1 cell membranes as camouflage. In tumors, CVOVM initiates a series of catalytic reactions: CoVO x promotes numerous ROS generation, while V-9302 disrupts glutamine metabolism, depleting glutathione (GSH) and nicotinamide adenine dinucleotide (NAD + ), thereby triggering the assembly of PANoptosome primarily composed of NLRP3 and NLRC5, which initiates pyroptosis, apoptosis, and necroptosis. The occurrence of PANoptosis promotes immunogenic cell death (ICD) to remodel tumor immunosuppressive microenvironment, and enhances immunotherapy and inhibits lung metastasis. Overall, we present a previously unreported mechanis to achieve the synergistic induction of PANoptosis through ROS amplification and metabolic inhibition, enhancing antitumor immunity, and potentially providing new opportunities and possibilities for combination cancer therapy.
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