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Nanomedicine · 2018 · IF 5.005

Hyperbaric oxygen as an adjuvant to temozolomide nanoparticle inhibits glioma growth by inducing G2/M phase arrest

Yuanyuan Xie,Xiaofan Zeng,Xian Wu,Jun Hu,Yanhong Zhu,Xiangliang Yang

Aim: To study the effects of combinational treatment of hyperbaric oxygen (HBO) and nanotemozolomide in glioma. Materials & methods: Temozolomide (TMZ)-loaded porous silicon nanoparticles (TMZ/PSi NPs) were prepared. In vitro and in vivo evaluations were performed. Results: The cell uptake of TMZ/PSi NPs could be tracked by autofluorescence of porous silicon. The concentration of oxygen in tumor was improved and the antitumor rate was increased to 84.2% in the TMZ/PSi NPs combined with HBO group. The viability of hypoxia-induced glioma C6 cells was decreased and cell cycle was arrested at G2/M phase in response to TMZ/PSi NPs treatment with HBO compared with continuous treatment with hypoxia. Conclusion: The combinational treatment of TMZ/PSi NPs and HBO could be a promising therapeutic strategy for glioma.

CAS / MDL: 85622-93-1
研究领域: 肿瘤学 · 药理学 · 神经科学
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Exploration · 2025 · IF 22.5

Hyperbaric Oxygen Regulates Tumor pH to Boost Copper-Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells

Qingyuan Deng,Ao Hua,Shiyou Li,Zhijie Zhang,Xiang Chen,Qiang Wang,Xing Wang,Zhiqin Chu,Xiangliang Yang,Zifu Li

An extracellular acidic environment and an intracellular mildly alkaline environment induced by carbonic anhydrase 9 (CA9) play a critical role in self-renewal, invasion, migration, and drug resistance of cancer stem cells (CSCs) within hypoxic solid tumors. Here, we report an antitumor strategy leveraging hyperbaric oxygen therapy (HBO) to regulate tumor pH and boost hydroxyethyl starch-doxorubicin-copper nanoparticles (HHD-Cu NPs) against CSCs. HBO overcomes tumor hypoxia, downregulates pH-regulatory proteins such as CA9, and leads to intracellular accumulation of acidic metabolites. As a result, HBO promotes intracellular acidification of both tumor cells and CSCs, triggering efficient doxorubicin release and the potent copper-mediated chemical dynamic effect of subsequently administered dual-acid-responsive HHD-Cu NPs. The combination of HBO with HHD-Cu NPs not only eliminates tumor cells but also inhibits CSCs, altogether leading to potent tumor inhibition. This study explores a new function of clinical-widely used HBO and establishes a novel combination therapy for treating CSCs abundant hypoxic solid tumors.

CAS / MDL: 3317-61-1 7447-39-4
研究领域: 肿瘤学 · 生物医学工程 · 药理学
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JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY · 2022 ·Vol. 149 ·期 2 ·683-699 · IF 4.322

Hyperbaric oxygen enhanced the chemotherapy of mitochondrial targeting molecule IR-780 in bladder cancer

Shen Chongxing,Yue Xiaofeng,Dai Linyong,Wang Jianwu,Li Jinjin,Fang Qiang,Zhi Yi,Shi Chunmeng,Li Weibing

Background Bladder cancer has a high rate of recurrence and drug resistance due to the lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types and exhibited tumor-killing effects in some cancers. However, this therapeutic strategy is rarely studied in bladder cancer. Material and methods The accumulation of IR-780 in bladder cancer was measured by NIR imaging. Human bladder cell lines (T24, 5637, and TCCSUP) were treated with IR-780 or combined IR-780 and hyperbaric oxygen (HBO). Cell viability, cell apoptosis, cellular ATP production, mitochondrial reactive oxygen species (ROS), and plasma membrane potential were detected. Mitochondrial complex I protein NDUFS1 was measured by western blot. To confirm the anti-tumor efficacy of IR-780 + HBO, mouse bladder cell line (MB49) tumor-bearing mice were established and tumor size and weight were recorded. Besides, cell apoptosis and tumor size were assessed in drug-resistant bladder cancer cells (T24/DDP) and xenografts to evaluate the effect of IR-780 + HBO on drug-resistant bladder cancer. Results IR-780 selectively accumulated in bladder cancer (bladder cancer cells, transplanted tumors, and bladder cancer tissue from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. The combination with HBO could significantly enhance the anti-tumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial ROS production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. Conclusion We identified for the first time a combination of IR-780 and HBO (IR-780 + HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.

CAS / MDL: 25316-40-9 14913-33-8
研究领域: 肿瘤学 · 药理学 · 分子生物学 · 细胞生物学
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Nature Communications · 2024 ·Vol. 15 ·期 1 ·1-21 · IF 14.7

Hyperbaric oxygen enhances tumor penetration and accumulation of engineered bacteria for synergistic photothermal immunotherapy

Xu Ke-Fei,Wu Shun-Yu,Wang Zihao,Guo Yuxin,Zhu Ya-Xuan,Li Chengcheng,Shan Bai-Hui,Zhang Xinping,Liu Xiaoyang,Wu Fu-Gen

Bacteria-mediated cancer therapeutic strategies have attracted increasing interest due to their intrinsic tumor tropism. However, bacteria-based drugs face several challenges including the large size of bacteria and dense extracellular matrix, limiting their intratumoral delivery efficiency. In this study, we find that hyperbaric oxygen (HBO), a noninvasive therapeutic method, can effectively deplete the dense extracellular matrix and thus enhance the bacterial accumulation within tumors. Inspired by this finding, we modify Escherichia coli Nissle 1917 (EcN) with cypate molecules to yield EcN-cypate for photothermal therapy, which can subsequently induce immunogenic cell death (ICD). Importantly, HBO treatment significantly increases the intratumoral accumulation of EcN-cypate and facilitates the intratumoral infiltration of immune cells to realize desirable tumor eradication through photothermal therapy and ICD-induced immunotherapy. Our work provides a facile and noninvasive strategy to enhance the intratumoral delivery efficiency of natural/engineered bacteria, and may promote the clinical translation of bacteria-mediated synergistic cancer therapy.

研究领域: 肿瘤学 · 生物医学工程 · 免疫疗法
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JOURNAL OF NANOBIOTECHNOLOGY · 2019 ·Vol. 17 ·期 1 ·1-12 · IF 5.345

Mild thermotherapy and hyperbaric oxygen enhance sensitivity of TMZ/PSi nanoparticles via decreasing the stemness in glioma

Zeng Xiaofan,Wang Qi,Tan Xuan,Jia Le,Li Yuwei,Hu Mingdi,Zhang Zhijie,Bai Xicheng,Zhu Yanhong,Yang Xiangliang

Background Glioma is a common brain tumor with a high mortality rate. A small population of cells expressing stem-like cell markers in glioma contributes to drug resistance and tumor recurrence.Methods Porous silicon nanoparticles (PSi NPs) as photothermal therapy (PTT) agents loaded with TMZ (TMZ/PSi NPs), was combined with hyperbaric oxygen (HBO) therapy in vitro and in vivo. To further investigate underlying mechanism, we detected the expression of stem-like cell markers and hypoxia related molecules in vitro and in vivo after treatment of TMZ/PSi NPs in combination with PTT and HBO.Results NCH-421K and C6 cells were more sensitive to the combination treatment. Moreover, the expression of stem-like cell markers and hypoxia related molecules were decreased after combination treatment. The in vivo results were in line with in vitro. The combination treatment presents significant antitumor effects in mice bearing C6 tumor compared with the treatment of TMZ, PTT or TMZ/PSi NPs only.Conclusion These results suggested the TMZ/PSi NPs combined with HBO and PTT could be a potential therapeutic strategy for glioma.

CAS / MDL: 85622-93-1
研究领域: 肿瘤学 · 纳米技术 · 治疗策略
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Journal of Integrative Neuroscience · 2025 ·Vol. 24 ·期 7 ·39656 · IF 2.7

Effect of Hyperbaric Oxygen Treatment on Lipid Metabolism and Neurovascular Microenvironment in an Apolipoprotein E Knockout Mouse Model

Guoying Dong,Yuxiao Liu,Huijun Liu,Chen Qiao,Xia Chen,Linxiao Wang

Background:Dyslipidemia during midlife represents a significant risk factor for neuropathological alterations associated with cognitive decline. Given the currently incurable nature of dementia, implementation of preventive strategies and early therapeutic interventions prior to disease progression are paramount. Emerging evidence suggests that hyperbaric oxygen (HBO) therapy exhibits neuroprotective properties in various neurological conditions. However, whether HBO treatment modulates lipid metabolism dysregulation and subsequent neurodegeneration remains unanswered. This investigation aimed to elucidate the therapeutic potential of HBO treatment in ameliorating cerebral dysfunction and metabolic perturbations using apolipoprotein E (ApoE)-deficient (ApoE-/-) mice.Methods:ApoE-/- mice received HBO treatment for 10 consecutive days, and then behavioral assessment tests were performed. Serum and brain tissue were collected to measure oxidative stress levels and inflammatory factors.Results:Compared with ApoE-/- group, cognitive declines was significantly reversed in mice of the ApoE-/-+HBO mice. The blood lipid profiles of ApoE-/- mice were also improved after HBO treatment, accompanied by a reduction in body weight. Moreover, HBO treatment was found to ameliorates neuronal injury and amyloid-β deposition in the hippocampus of ApoE-/- mice. Further studies have revealed that the benefits of HBO treatment occurred through the reduction of inflammatory factors and attenuation of oxidative stress.Conclusions:These findings indicate that HBO treatment effectively improves the intracerebral microenvironment of ApoE-/- mice, providing a novel regulatory mechanism of protection against dyslipidemia-associated brain deficits by HBO treatment.

CAS / MDL: 517-28-2 64-17-5 92-31-9
研究领域: 神经病学 · 代谢紊乱 · 生物医学研究 · 炎症反应 · 氧化应激 · 行为神经科学
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Research · 2024 · IF 8.5

Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism

Chen Xiao,Jiayuan Li,Ao Hua,Xing Wang,Shiyou Li,Zheng Li,Chen Xu,Zhijie Zhang,Xiangliang Yang,Zifu Li

Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resist cuproptosis-induced mitochondria damage. Here, we leverage hyperbaric oxygen (HBO) to regulate CSC metabolism by overcoming tumor hypoxia and to augment CSC elimination efficacy of polydopamine and hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@PH NPs). Mechanistically, while HBO and CuET@PH NPs inhibit glycolysis and oxidative phosphorylation, respectively, the combination of HBO and CuET@PH NPs potently suppresses energy metabolism of CSCs, thereby achieving robust tumor inhibition of PDAC and elongating mice survival importantly. This study reveals novel insights into the effects of cuproptosis nanomedicine on PDAC CSC metabolism and suggests that the combination of HBO with cuproptosis nanomedicine holds significant clinical translation potential for PDAC patients.

研究领域: 肿瘤学 · 纳米技术 · 药理学 · 分子生物学
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ADVANCED MATERIALS · 2023 · IF 29.4

A Programmable Oxygenation Device Facilitates Oxygen Generation and Replenishment to Promote Wound Healing

Jumin Yang,Xin Jin,Wenguang Liu,Wei Wang

Inadequate oxygenation is one of the chief culprits for delayed wound healing. However, current oxygen therapies, such as hyperbaric oxygen therapy and topical oxygen therapy, face hurdles in providing sustained and long-term oxygenation to reverse wound hypoxia. Furthermore, their efficacy in rejuvenating wound injury is restricted by limited penetration of oxygen in the wound bed. Herein, this study proposes a programmable and portable oxygenation device (named GUFO oxydevice) by ingeniously integrating (i) a controllable oxygen generation and unidirectional transmission system (COGT-UTS), and (ii) a supramolecular assembled perfluorinated hyperbranched polymer/gelatin (GUF) hydrogel in which the perfluorinated hyperbranched polymer (FHBP) acts as an oxygen reservoir to ensure sustained and convenient oxygen replenishment and thus directly regulate the hypoxic wound microenvironment. Accelerating the wound healing process by GUFO oxydevice was achieved in both a diabetic rat and an acute porcine wound model without any secondary tissue damages. The present study demonstrates that the GUFO oxydevice holds promise as a practically feasible candidate for wound treatment. This article is protected by copyright. All rights reserved

研究领域: 生物医学工程 · 组织工程 · 伤口愈合 · 材料科学 · 药学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Hyperbaric oxygen augments chemodynamic effect induced by probiotic-derived selenium nanoparticles to enhance cancer immune checkpoint blockade therapy

Puze Li,Yuzhu Yao,Xue Chen,Cheng Song,Meichan Wu,Jinzhao Huang,Dongdong Wang,Xuyu Li,Ban Luo,Xiangliang Yang,Jun Hu

Chemodynamic therapy (CDT) was a promising approach to enhance the immunogenicity of tumor cells for potentiating immune checkpoint blockade (ICB) therapy, but usually suffered from hypoxia and immunosuppressive tumor microenvironment. Herein, we developed a hyperbaric oxygen (HBO)-strengthened CDT-nanoadjuvants platform (Se@OMV-GOx-HA) by modifying probiotic-derived selenium (Se) nanoparticles with glucose oxidase (GOx) and hyaluronic acid (HA) to boost αPD-L1-medaited ICB therapy against breast cancer. In the presence of H 2 O 2 and glutathione (GSH), Se@OMV acted as nanoenzyme to mediate the electron transfer from GSH to O 2 giving O 2 – , while GOx catalyzed the production of H 2 O 2 . Synergistically, HBO effectively improved tumor hypoxia to foster GOx-catalyzed oxidation of glucose to H 2 O 2 , then provided the essential fuels including H 2 O 2 and O 2 for Se-mediated O 2 – generation, causing strong immunogenic cell death (ICD) effect to enhance the immunogenicity of tumor cells. Under co-stimulation by Se@OMV acting as immunoadjuvants, maturation of dendritic cells and priming of cytotoxic T cells were largely promoted. Assisted by HBO, infiltration of cytotoxic T cells in mice tumor was significantly improved, which not only generated long-term antitumor immune memory, but largely boosted αPD-L1-medaited ICB therapy. Given the clinical available of HBO, this nanosystem has great clinical translation potential for cancer CDT/immunotherapy.

研究领域: 癌症治疗 · 纳米技术 · 免疫学 · 肿瘤学
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