Advanced Science
·
2026
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IF 14.1
Tianhua Xiao,Zunlei Gong,Chuke Chen,Hui Yu,Yu Cai,Can Liu,Hongkai Huang,Ying Li,Jinyuan Guan,Le Wang,Chengyun Ning,Guoxin Tan,Lei Zhou
Radiotherapy (RT) is widely used as an adjuvant treatment after surgical resection for osteosarcoma, but its efficacy is often limited by insufficient radiosensitization and an immunosuppressive tumor microenvironment that restricts systemic antitumor immunity and promotes recurrence and metastasis. Here we report an injectable metal‐drug supramolecular condensate formed from hafnium ions and alendronate (Hf‐ALN) and loaded with the COX‐2 inhibitor celecoxib (CXB) for synergistic radioimmunotherapy of postoperative osteosarcoma. The condensate forms through coordination‐driven liquid‐liquid phase separation between Hf 4+ ions and alendronate, enabling local retention within postoperative bone defects and sustained therapeutic release. Upon X‐ray irradiation, the Hf component amplifies radiation energy deposition and reactive oxygen species generation, thereby enhancing radiation‐induced DNA damage and immunogenic cell death. Meanwhile, the acidic tumor microenvironment triggers responsive release of CXB and ALN; CXB inhibits the COX‐2/PGE 2 immunosuppressive pathway, while ALN promotes macrophage repolarization toward the M1 phenotype, collectively remodeling the tumor immune microenvironment. This strategy enhances dendritic cell maturation, activates cytotoxic CD8 + T cells, and reduces regulatory T‐cell infiltration. In orthotopic osteosarcoma models, CXB@Hf‐ALN combined with RT suppresses tumor recurrence, preserves bone integrity, inhibits pulmonary metastasis, and prolongs survival with minimal systemic toxicity, offering a promising strategy to improve postsurgical RT outcomes in osteosarcoma. This work designed an injectable metal‐drug supramolecular condensate formed from hafnium ions and alendronate (Hf‐ALN) and loaded with the COX‐2 inhibitor celecoxib (CXB) for synergistic radioimmunotherapy of postoperative osteosarcoma. Mechanistically, upon X‐ray irradiation, Hf enhances radiation energy deposition, ROS generation, and DNA damage, while CXB blocks COX‐2/PGE 2 and ALN repolarizes M1 macrophages, remodeling immune microenvironment to inhibit recurrence/metastasis and preserve bone integrity.
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PubMed
高影响因子
Materials
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2026
·Vol. 19
·期 10
·2086
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IF 3.7
Dazhong Jin,Miaomiao He,Guangfu Yin
Surgical intervention is a primary treatment for osteosarcoma, often resulting in a tumorous bone defect with an irregular shape. Postoperative management is essential to minimize tumor recurrence risks and promote bone regeneration. To address these issues, we developed a multifunctional injectable, rapidly photo-curable hydrogel composed of gelatin methacryloyl/carboxymethyl chitosan/hyaluronic acid (GelMA/CMCS/HA), modified with vanadium-doped mesoporous bioactive glass (VMBG). The exceptional injectability enables seamless adaptation to irregular bone defects, offering a significant advantage over preformed implants, while the rapid photocurability of the hydrogel ensures stable fixation within minutes, thereby reducing potential risks during surgery. Furthermore, this platform exhibits dual therapeutic efficacy, characterized by antitumor activity and osteogenic induction. In vitro assessments demonstrated that V(V)/V(IV) valence cycling-driven ROS generation mediated its potent antitumor efficacy. Additionally, concurrent enhancement of alkaline phosphatase activity and osteogenic marker expression validated its osteogenic potential. The CMCS incorporation promoted healing at the defect site, while the HA addition created binding sites for cell adhesion and growth, thereby improving scaffold bioactivity. Collectively, this study presents the development and validation of a multifunctional GelMA/CMCS/HA hydrogel, highlighting its dual capability for bone regeneration and tumor suppression within tumor-associated bone microenvironments.
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PubMed
高影响因子
Biomaterials Advances
·
2026
·
IF 6.7
Yong Zheng,Yong Tao,Fuqiang Tan,Keyi Feng,Fei Xie,Shasha Shi,Yunsheng Ou
In vitro : CPP reduced 143B cell viability by ~50% at 30 µg/mL with low toxicity to normal osteoblasts. • In vivo : CPP reduced xenograft tumor volume by ~80% and showed good biosafety in histology and serum tests. • Mechanism: CPP induced ROS accumulation, GSH depletion, SLC7A11/GPX4 downregulation, and ferroptotic mitochondrial damage. Ferroptosis induction represents a promising antitumor strategy, yet osteosarcoma cells frequently resist ferroptosis through the PSMD14-mediated stabilization of SLC7A11. Here, we report an acid-responsive cobalt-doped ZIF-8 nanoplatform loaded with 1, 10-phenanthroline and coated with PEG (denoted as CPP) that simultaneously amplifies oxidative stress and dismantles the PSMD14/SLC7A11 antioxidant axis. Upon exposure to the acidic tumor microenvironment, the ZIF-8 framework degrades, releasing Co 2+ ions that catalyze Fenton-like reactions to generate hydroxyl radicals (•OH) and initiate lipid peroxidation. Concurrently, 1, 10-phenanthroline chelates the catalytic Zn 2+ of PSMD14, abolishing its deubiquitinase activity and thereby promoting ubiquitin-dependent degradation of SLC7A11, which depletes intracellular glutathione (GSH). Physicochemical characterization confirmed the successful construction of CPP nanoparticles (~100 nm) with a drug loading efficiency of 14.76% and pH-triggered Co 2+ release. In vitro , CPP was efficiently internalized by 143B osteosarcoma cells and exhibited dose-dependent cytotoxicity with markedly elevated reactive oxygen species (ROS), malondialdehyde (MDA) accumulation, lipid peroxidation, mitochondrial depolarization, and downregulation of SLC7A11 and GPX4, collectively supporting ferroptosis. CPP also significantly suppressed osteosarcoma cell invasion. In a subcutaneous 143B xenograft model, intravenous CPP administration reduced tumor volume by approximately 80% relative to controls, with pronounced tumor necrosis, proliferation inhibition, and decreased SLC7A11/GPX4 expression in tumor tissues, while maintaining favorable biosafety. These findings establish CPP as a dual-action nanoplatform for ferroptosis-based osteosarcoma therapy.
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高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Yilin Wang,Yufeng Yuan,Wei Liao,Zaikai Zhuang,Xueying An,Bo Jiang,Chaofeng Zhang,Sehrish Manan,Peng Wang,Yongcan Jin
Lignin, a complex biopolymer, has promising biomedical applications due to its unique structure and chemical modifiability. This study shows that lignin modified with hydroxyl and carboxyl groups enhances GSH adsorption, thereby improving cytotoxicity and selectivity against osteosarcoma. The modified lignin induces mitochondrial dysfunction via mPTP activation, resulting in membrane depolarization, cytochrome c release, and ATP depletion, ultimately triggering the pro-apoptotic protein BAX and downregulation of the antiapoptotic protein BCL2. Moreover, lignin treatment significantly increased reactive oxygen species (ROS) levels while depleting intracellular GSH, further promoting oxidative stress-induced apoptosis. In vivo studies confirmed that lignin samples were effective in inhibiting tumor growth with a favorable biosafety profile. Among them, CML showed the strongest anticancer effect. These findings highlight the potential of modified lignin as a safe and effective therapeutic agent for OS treatment, offering a novel strategy to enhance oxidative-stress-mediated tumor cell apoptosis while sparing normal cells.
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高影响因子
BIOORGANIC CHEMISTRY
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2025
·
IF 4.7
Nan Li,Feng-xiang Pang,Yu-wan Zhou,Shou-chang Ding,Chuan-jian Shi,Rui-jia Wen,Yong-xin Mai,Xian-lin Wu,Jin-fang Zhang
Background Osteosarcoma (OS) is a malignant primary tumor in bone tissues, and Methotrexate (MTX) is widely used as a chemotherapeutic drug for OS in clinical treatment. However, MTX resistance is a major challenge for OS patients. Polydatin (PD) is an extract derived from Reynoutria japonica Houtt and has been identified as a potential agent for reversing chemotherapy resistance in cancer. We therefore wondered whether PD could alleviate MTX resistance in OS. Methods The effect of PD on MTX resistance was investigated. And H19 expression was examined in the PD-treated OS cells. The association between H19 and MTX resistance in osteosarcoma was investigated.The effects of H19 on MTX resistance in osteosarcoma were evaluated by cell proliferation, colony formation, ChIP and western blotting assays. In order to investigate the molecular mechanism of PD underlying methotrexate resistance in OS, the cell proliferation, colony formation, q-PCR and western blotting were examined. Results In the present study, PD was found to act as a novel MTX sensitizer, and significantly enhanced the suppressive effects of MTX on OS in vitro and in vivo . Mechanically, PD was demonstrated to suppress the expression of long non-coding RNA H19 as well as its binding protein histone methyltransferase Enhancer of zeste homolog 2 (EZH2), and thus reduced the trimethylation of histone H3K9 (H3K9me3) and K27 (H3K27me3). Furthermore, H19 knowndown increased the binding ability of H3K9me3 and H3K27me3 with the folate metabolism-related genes RFC-1 and PCFT's promoter, and influenced folate metabolism and MTX resistance. Conclusion In conclusion, our results indicated that PD alleviated MTX resistance in OS via the H19/H3K27me3/H3K9me3 mediated folate metabolism regulatory axis. The translational potential of this article The findings of this study validate the function of PD in alleviating MTX resistance, and provide the new insight into developing PD as a promising drug candidate for the MTX resistant OS patients.
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Jian Wang,Peirong Xu,Yeyong Zhang,Shuai Han,Gongteng Wang,Hangxiang Wang,Haihan Song,Shufeng Li
Summary Supramolecular prodrug self-assembly is a cost-effective and powerful approach for creating injectable anticancer nanoassemblies. Herein, we describe the self-assembly of small-molecule prodrug nanotherapeutics for tumor-restricted pharmacology that can be self-activated and independent of the exogenous stimuli. Covalent dimerization of the anticancer agent cabazitaxel via reactive oxygen species (ROS)- and esterase-activatable linkages produced the homodimeric prodrug diCTX, which was further coassembled with an ROS generator, dimeric dihydroartemisinin (diDHA). The coassembled nanoparticles were further refined in an amphiphilic matrix, making them suitable for in vivo administration. The ROS obtained from the coassembled diDHA synergized with intracellular esterase to activate the neighboring diCTX, which in turn induced potent cytotoxicity. In a preclinical orthotopic model of human osteosarcomas, nanoparticle administration exhibited durable antitumor efficacy. Furthermore, this smart, dual-responsive nanotherapeutic exhibited lower toxicity in animals than those of free drug combinations. We predict that this platform has great potential for further clinical translation.
研究领域:
肿瘤学
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药剂学
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纳米医学
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DOI
高影响因子
Small
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2024
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IF 13
Jiabao Dong,Xupeng Chai,Yucheng Xue,Shiyun Shen,Zhuo Chen,Zetao Wang,Eloy Yinwang,Shengdong Wang,Liang Chen,Fengfeng Wu,Hengyuan Li,Zehao Chen,Jianbin Xu,Zhaoming Ye,Xiongfeng Li,Qian Lu
Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.
研究领域:
癌症生物学
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药学
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免疫治疗
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PubMed
高影响因子
International Journal of Nanomedicine
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2025
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IF 6.5
Molin Li,Yufei Ma,Hui Yao,Hao Jia,Yalan Wang,Xuefeng Tang
Purpose Osteosarcoma poses significant clinical challenges due to its high recurrence, metastatic potential, and poor prognosis. Celastrol (CLT), known for its antitumor, immunomodulatory, and osteogenic regulatory properties, has garnered substantial interest. Developing a targeted CLT delivery system is critical to enable precise drug release, integrate photothermal therapy, remodel the tumor microenvironment, and improve post-surgical treatment and repair in osteosarcoma.Methods Using emulsion-induced interface assembly, we synthesized mesoporous polydopamine-polyethylene glycol (MPDA-PEG) nanospheres and loaded them with celastrol to fabricate the targeted system MPDA-PEG-CLT. We characterized the nanospheres’ physicochemical properties and evaluated MPDA-PEG-CLT’s efficacy in synergistic drug-photothermal therapy for osteosarcoma through in vitro and in vivo experiments.Results MPDA-PEG-CLT achieved a drug loading capacity of ~14% and a photothermal conversion efficiency of 37.6% under 808 nm NIR irradiation, which enhanced celastrol release. The system induced osteosarcoma cell apoptosis, promoted bone marrow mesenchymal stem cell (BMSC) differentiation, and ameliorated the lesion microenvironment, resulting in efficient tumor ablation in mice.Conclusion MPDA-PEG-CLT significantly enhances celastrol’s targeted delivery efficiency, promotes mitochondrial apoptosis in osteosarcoma cells, synergizes with photothermal therapy to eradicate tumors, and improves the bone tissue microenvironment in lesions. This system offers a promising strategy for post-surgical osteosarcoma treatment and repair.
研究领域:
肿瘤学
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纳米医学
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生物材料
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转化医学
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药剂学
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分子肿瘤学
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再生医学
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
·
IF 9.7
Guanhong Liu,Rongze Tang,Congcong Wang,Dehong Yu,Zhenxin Wang,Haochen Yang,Jia Wei,Shunhua Zhu,Fenglei Gao,Feng Yuan,Bin Pan
Cuproptosis and ferroptosis are difficult to synergize in tumor suppression due to their spatiotemporal asynchrony and mechanistic dispersion. Therefore, we proposed a new paradigm of Ferroptosis-Cuproptosis self-recycling. An iron‑sulfur cluster (Fe-S) metabolic collapse was constructed by hyaluronic acid (HA)-functionalized bimetallic nano-enzymes (HA@CuCo-NC) to initiate this tumoricidal mechanism. HA@CuCo-NC specifically accumulates in osteosarcoma cells through HA-mediated targeting. The multi-enzyme activity triggers a surge of reactive oxygen species (ROS) in the tumor microenvironment, which, along with Co 2+ , induces ferroptosis. This leads to severe mitochondrial damage and glutathione (GSH) depletion, which in turn activates the cuproptosis cascade. Cuproptosis causes Fe-S protein degradation and Fe 2+ release into the labile iron pool (LIP) by inhibiting Fe-S cluster formation and dihydrolipoamide acetyltransferase (DLAT) oligomerization. The released Fe 2+ enhances oxidative stress and promotes membrane disassembly via the Fenton reaction. The two act synergistically to form a dynamic self-reinforcing cycle: Ferroptosis-related mitochondrial damage exacerbates the toxicity of Cu 2+ . Cuproptosis-released Fe 2+ further activates ferroptosis. In vivo experiments demonstrated that HA@CuCo-NC significantly inhibited the growth of osteosarcoma in situ without causing systemic toxicity. This research introduces a novel approach to treating solid tumors by reconstructing the metabolic interaction network of copper and iron.
研究领域:
肿瘤学
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纳米医学
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分子生物学
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细胞死亡机制
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金属代谢
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转化医学
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氧化应激
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PubMed
高影响因子
Bioactive Materials
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2024
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IF 18
Cairong Xiao,Renxian Wang,Rumin Fu,Peng Yu,Jianxun Guo,Guangping Li,Zhengao Wang,Honggang Wang,Jingjun Nie,Weifeng Liu,Jinxia Zhai,Changhao Li,Chunlin Deng,Dafu Chen,Lei Zhou,Chengyun Ning
Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO 3 ), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.
研究领域:
生物医学工程
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纳米技术
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癌症治疗
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组织工程
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材料科学
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PubMed
高影响因子
Biomaterials Advances
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2024
·
IF 5.5
Yang Yang,Jian Cao,Hongmei Gu,Jiajia Liu,Jianhua Xue,Qiang Xue,Xianchen Liu,Yong Hu
Chemodynamic therapy (CDT) has played an important role in osteosarcoma (OS) treatment. However, the insufficient content of endogenous H 2 O 2 and high expression of glutathione (GSH) in tumor tissues limit the antitumor efficacy of CDT. In this work, we developed polydopamine (PDA) coated and CuO 2 NPs loaded ZIF8 nanoparticles (CuO 2 @ZIF8@PDA NPs) for thermally reinforced CDT treatment of OS. The CuO 2 @ZIF8@PDA NPs exhibited excellent stability in neutral solutions while degraded in weakly acidic environments to generate hydrogen peroxide (H 2 O 2 ) and Cu 2+ . Cu 2+ consumes GSH in tumor tissues to generate Cu + . Both Cu 2+ and Cu + catalyzed the decomposition of H 2 O 2 , triggering a Fenton-like reaction to produce hydroxyl radicals (•OH). The PDA coating endowed the nanosystem with photothermal conversion capabilities under near-infrared laser irradiation, further promoting the generation of •OH, and inducing tumor cell death. In vitro experiments demonstrated that CuO 2 @ZIF8@PDA NPs exhibited significant toxicity towards K7M2 cells while remaining non-toxic to normal cells. In vivo studies revealed that under 808 nm laser irradiation, CuO 2 @ZIF8@PDA NPs exhibited stronger killing ability against K7M2 cells than CuO 2 @ZIF8@PDA NPs alone. This system, which combines GSH depletion, intratumoral H 2 O 2 self-generation, and photothermally enhanced CDT, holds great promise for playing a pivotal role in the treatment of osteosarcoma.
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物医学工程
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PubMed
高影响因子
MATERIALS & DESIGN
·
2025
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IF 7.9
Feipeng Wu,Weiling Yin,Hui Shan,Jie Cang,Ruixing Shui,Xianwen Yan,Wenbo He,Junmeng Liu,Jia Gao,Dapeng Li,Guoqing Pan
Osteosarcoma (OS) constitutes a highly malignant bone tumor, prone to postoperative recurrence and marked bone loss, which presents substantial challenges to current clinical practice. To address these difficulties, we developed a dynamic hydrogel constructed via reversible Cu–S coordination bonds, endowed with injectability, self-healing capacity, and biodegradability.This hydrogel is composed of copper sulfide nanoparticles (CuS 2 NPs), thiolated osteogenic peptide (OGP-SH), and thiolated biomacromolecular gelatin (Gel-SH). The incorporation of copper sulfide nanoparticles imparts strong photothermal conversion properties to the hydrogel, enabling effective ablation of residual osteosarcoma cells upon irradiation with 808 nm near-infrared (NIR) light. Concurrently, the sustained release of osteogenic peptide and trace amounts of copper ions facilitates osteogenic differentiation and promotes bone regeneration. The hydrogel demonstrated excellent injectability, structural stability, rheological recovery capacity, as well as favorable biocompatibility, with a degradation rate of approximately 65 % within 14 days. The results of in vitro and in vivo studies substantiated its dual functionality in suppressing tumor recurrence and enhancing bone repair. The research data reveal that this hydrogel exhibits broad prospects as a multifunctional therapeutic vehicle for postoperative osteosarcoma management and skeletal tissue regeneration.
研究领域:
生物医学工程
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纳米医学
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癌症治疗
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组织工程
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生物材料
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高影响因子
危险品化学品经营许可证（带存储）