Materials Today Bio
·
2024
·
IF 8.7
Lin Ye,Congcong Yu,Jiechao Xia,Kainan Ni,Yejin Zhang,Xiaozhang Ying,Dingqi Xie,Yang Jin,Rongtai Sun,Ruikang Tang,Shunwu Fan,Shasha Yao
Reactive Oxygen Species (ROS) refers to a highly reactive class of oxidizing species that have the potential to induce cellular apoptosis and necrosis. Cuproptosis, a type of cell death, is primarily associated with the effects of copper ions. However, the specific relationship between ROS, cuproptosis, and osteosarcoma (OS) remains relatively unexplored. Additionally, there is limited research on the use of cuproptosis in conjunction with oxidative stress for treating OS and inhibiting tumor-induced bone destruction. To address these gaps, a novel treatment approach has been developed for OS and neoplastic bone destruction. This approach involves the utilization of glutathione (GSH) and pH-responsive organic-inorganic mesoporous silica nanoparticles@Cu 2 S@oxidized Dextran (short for MCD). The MCD material demonstrates excellent cytocompatibility, osteogenesis, tumor suppression, and the ability to inhibit osteoclast formation. The specific mechanism of action involves the mitochondria of the MCD material inhibiting key proteins in the tricarboxylic acid (TCA) cycle. Simultaneously, the generation of ROS promotes this inhibition and leads to alterations in cellular energy metabolism. Moreover, the MCD biomaterial exhibits promising mild-temperature photothermal therapy in the second near-infrared (NIR-II) range, effectively mitigating tumor growth and OS-induced bone destruction in vivo .
研究领域:
肿瘤学
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生物医学工程
·
药理学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Yangjun Feng,Xiao He,Yameng Wang,Zhiyuan Wang,La Ta,Yunshu Han,Xue Ke
Mn-coordinated liposomes (AC@MLip-IL11) promote cellular uptake and lysosomal escape. • Mn 2+ and ADU-S100 activate STING, celastrol relieves AKT-mediated inhibition. • AC@MLip-IL11 induces ICD and activates STING, triggering antitumor immune responses. • AC@MLip-IL11 Gel effectively inhibits subcutaneous post-operative recurrence of OS. Surgical resection remains the standard treatment regimen for osteosarcoma (OS). However, residual tumor cells and postoperative immunosuppression frequently induce tumor recurrence and metastasis. Although STING agonist-based immunotherapy offers a promising strategy for postoperative treatment, its efficacy is limited by a narrow therapeutic window, susceptibility to enzymatic degradation, and negative regulatory mechanisms. To address these challenges, this study developed a manganese (Mn)-coordinated liposome (ADU-S100/celastrol@MnLip-IL11, AC@MLip-IL11) composite hydrogel to enhance local immunotherapeutic efficacy for post-resection OS. The core design of this system encompasses three aspects: (1) drug reservoir, whereby the hydrogel achieves sustained release, enabling prolonged therapeutic efficacy; (2) potent activation, as AC@MLip-IL11 promotes efficient cellular uptake and lysosomal escape, while Mn 2+ acts synergistically with ADU-S100 to “press the accelerator” for STING pathway activation; and (3) synergistic potentiation, whereby celastrol not only induces mitochondrial damage but also “releases the brake” on STING signaling by blocking AKT-mediated negative regulation. This “press-accelerator, release-brake” synergistic strategy promotes tumor apoptosis, triggers efficient STING signaling, promotes abundant type I interferon secretion, facilitates dendritic cell maturation, and elicits CD8 + T cell-mediated antitumor immune responses, demonstrating significant therapeutic efficacy in preventing tumor recurrence in a subcutaneous postoperative OS mouse model. In summary, this study provides a versatile engineered platform for the development of cancer immunotherapies and offers new intervention insights for postoperative tumor treatment. Download: Download high-res image (199KB) Download: Download full-size image
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DOI
高影响因子
Bio-Design and Manufacturing
·
2025
·Vol. 8
·期 3
·423-441
·
IF 7.6
Mi Xuelian,Ren Ya,Wang Hanbo,Qiang Lei,Kong Weiqing,Wang Hui,Yang Xue,Liu Yihao,Yang Han,Xiao Di,Ma Zhenjiang,Xu Guoxing,Zhang Changru,Wang Jinwu
In the current settings of osteosarcoma research and drug screening, in vitro three-dimensional (3D) models, which overcome the limitations of traditional models, are favored. In in vitro 3D models, tumor microenvironment simulation, particularly of the mechanical microenvironment, is crucial for estimating the biological effects of a tumor. However, current in vitro osteosarcoma model construction is often limited to a single mechanical signal, which fails to simulate the diversity of osteosarcoma mechanical stimuli. In this study, we utilized embedded bioprinting technology and the multiple response properties of calcium ions in soft and hard stiffness systems with osteosarcoma cell biological functions to construct an integrated gradient biomechanical signal-tailored osteosarcoma model (IGBSTOM). We achieved this by printing a fibrinogen bioink containing calcium ions and osteosarcoma tumor spheroids within an extracellular matrix composed of methacryloylated alginate, methacryloylated gelatin, thrombin, and transglutaminase, which is rich in polysaccharides and proteins and exhibits self-healing properties. Our in vitro and in vivo studies showed that the IGBSTOM enhanced tumor stemness, proliferation, and migration, and successfully reproduced the nest-like structure of tumors, providing an in vitro research platform that is more similar to the natural tumor than the existing models. This study proposes a novel IGBSTOM construction and provides a new strategy for the clinical understanding of tumor development, drug screening, and exploration of drug resistance and metastasis mechanisms.
研究领域:
肿瘤学
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生物医学工程
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细胞生物学
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DOI
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Jiewen Zheng,Zhen Zuo,Tao Zhang,Yaqi Wang,Hui Liu,Wanfu Li
This research introduces FAM (FeS2-AIPH@Membrane), a nanoparticle system that synergizes photothermal therapy (PTT), chemodynamic therapy (CDT), and thermodynamic therapy (TDT) for targeted cancer treatment. FAM utilizes FeS2 for photothermal conversion and AIPH for radical generation, encapsulated within a tumor cell membrane to enhance targeting and immune evasion. The synthesis of FeS2 with AIPH was optimized, yielding nanoparticles with excellent stability and photothermal properties. Designed to release drugs in acidic tumor environments, FAM increases cytotoxicity at the target site. Under NIR irradiation in vitro, FAM nanoparticles mediated tumor cell death through concurrent reactive oxygen species production and localized hyperthermia. Cellular uptake studies confirmed enhanced intracellular concentrations due to homologous targeting. In vivo tests on MNNG/HOS tumor-bearing mice showed that FAM significantly reduced tumor volumes without systemic toxicity. These results demonstrate FAM’s potential as a safe, effective cancer theranostics platform, integrating PTT, CDT, and TDT into a single treatment modality, offering a more targeted, efficient, and less invasive cancer treatment alternative.
研究领域:
肿瘤学
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纳米医学
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生物材料学
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产品关联
DOI
高影响因子
Journal of Advanced Research
·
2025
·
IF 13
Minyi Zhang,Qi Wang,Chen Li,Mengyao Chen,Chunhui Wang,Zikang Wang,Tao Xia,Chengqing Yi,Shuo Shi
Introduction Ion interference therapy has emerged as a promising new treatment for Osteosarcoma (OS). However, its efficacy is significantly restricted by inadequate hydrogen peroxide (H 2 O 2 ) under the complex tumor microenvironment (TME). Objectives This study aimed to supply sufficient H 2 O 2 to enhance tumor therapy efficacy and address the limitations associated with ion interference. Methods A hollow manganese dioxide (HMnO 2 ) nanoplatform loaded with calcium peroxide (CaO 2 ) (denoted as HMnO 2 @CaO 2 ) was evaluated for biosafety through hemolysis tests. The functionality of HMnO 2 @CaO 2 was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and cytometric analysis. Results Excessive Ca 2+ accumulation induces endoplasmic reticulum (ER) stress, enhances oxidative stress, and causes mitochondrial damage. Notably, Mn 2+ facilitates treatment monitoring through magnetic resonance imaging (MRI). Additionally, Mn 2+ -induced ferroptosis triggers an immune response that promotes the polarization of tumor-associated macrophages (TAMs), transforming the pro-tumoral M2 phenotype into the tumoricidal M1 phenotype, thereby enhancing the efficacy of immunotherapy. Conclusion In conclusion, HMnO 2 @CaO 2 nanoplatform enhances tumor therapy efficacy by overcoming ferroptosis limitations, inducing Ca 2+ overload, and boosting anti-tumor immunity. This strategy offers a promising approach to ion interference in the clinical translation of nanomedicines. Furthermore, it marks a significant advancement in osteosarcoma (OS) treatment and underscores the transformative potential of nanotechnology in medicine.
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jia Yao,Pengtao Chen,Dingqi Xie,Jianqingchen Chen,Xiao Lin,Yujin Xu
Radiotherapy (RT) is a widely used clinical treatment for cancer, leveraging ionizing radiation; however, some patients exhibit resistance to radiation due to insufficient reactive oxygen species (ROS) production. Copper-based nanomaterials represent a promising class of antitumor agents capable of generating abundant ROS. In this study, R837 and Cu2–xSe were incorporated into PLGA (50:50)20k-PEG2k-iRGD to develop a targeted nanomaterial for tumor therapy. These nanoparticles effectively induced cuproptosis, inhibited tumor cell proliferation, remodeled the tumor immune microenvironment (TME), and promoted immunogenic cell death (ICD), thereby enhancing the efficacy of PD-1 checkpoint blockade therapy (αPD-1). Furthermore, our results demonstrated that the Cu2–xSe(R837)-iRGD nanoformulations, in combination with radiotherapy, promoted the infiltration of CD8+ T cells and activated antitumor immune responses in vivo. In conclusion, our study confirmed that Cu2–xSe(R837)-iRGD nanoformulations combined with radiotherapy yielded promising therapeutic outcomes and held potential for clinical application in osteosarcoma (OS) treatment.
研究领域:
肿瘤学
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纳米医学
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免疫治疗
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辐射生物学
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生物无机化学
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Naoying Guan,Xinru Wang,Jian Ren,Lunzhu Wang,Chunlin Deng
Accurately diagnosing bone cancer lesions and implants is a major clinical challenge. Fluorescence imaging (FI) offers precise, sensitive real-time monitoring and eco-friendly traits, making it promising for clinical use. Current fluorescent indicators using hydroxyapatite (HA) face instability and toxicity issues. We proposed a fluorescent indicator based on red-emitting, water-soluble N-, B-, and F-doped carbon dots (N,B,F-CDs) with a fluorescence quantum yield (QY) of up to 21.94%. By expanding the conjugated structure through N→B–F bonding, the emission wavelength shifted toward the red spectrum. Chemical precipitation was used to nucleate HA on N,B,F-CDs, producing red-emitting N,B,F-CDs-hydroxyapatite (CDs-HA) nanocomposite particles and increasing the QY to 23.70%. CDs-HA do not affect normal cells but could be easily endocytosed by osteosarcoma cells, enabling tracing. This study introduced possibilities for creating fluorescent N,B,F-CDs structures and applying CDs-HA for clinical detection of osteosarcoma spread or postoperative residual tumor tissue. CDs-HA are highly promising for in vivo visualization and as drug carriers.
研究领域:
生物医学工程
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纳米技术
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肿瘤学
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材料科学
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生物成像
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产品关联
DOI
高影响因子
Discover Oncology
·
2025
·Vol. 16
·期 1
·1-23
·
IF 2.9
Jiang Yingcun,Song Chao,Yan Jiyuan,Luo Liang,Gao Silong,Jiang Feng,Wei Zhangchao,Chen Jinwen,Liu Zongchao,Ge Jianhua
Ferroptosis has been demonstrated to have a significant role in osteosarcoma (OS), a highly aggressive and invasive malignant bone tumor. Nevertheless, the precise molecular mechanism underlying OS remains unknown. Understanding the makeup of the immune microenvironment in OS is crucial for its therapy, as the disease grows in the highly specialized, complex, and dynamic bone microenvironment. Resveratrol (Res) possesses anti-inflammatory, immunomodulatory, chemopreventive, antioxidant, and anticancer properties, it is unknown if it can modify ferroptosis to prevent OS. This time, using single-cell analysis and other bioinformatic studies, we will clarify the targets and composition of the immunological microenvironment of the ferroptosis process in OS, as well as the role of certain transcription factors in it. Ultimately, network pharmacology and vitro experiment have led to the initial identification of the molecular processes governing ferroptosis in OS, which are regulated by Res. The findings suggested the potential use of ALB, EGFR, GPX4, IL6, STAT3, and PTEN as OS prognostic and diagnostic biomarkers. Chondroblastic, myeloid cells, osteoblastic OS, CD4 + T, NK, CD8 + T, B cells, M1 macrophages, Chondro_Proli, etc. made up the majority of the immunological microenvironment of OS. The entire cellular trajectory demonstrates that immune cells infiltrating during the early stages of OS are mostly CD4 + T, NK, CD8 + T, B_cell, and M1 macrophages. This affects the development of myeloid cells and chondroblastic cells, which ultimately leads to the progression of highly malignant chondro cells to OS. Numerous pathways allow transcription factors including BCLAF1, MAF, SP1, TCF12, KLF11, and KMT2D to contribute to the development of tumors. Finally, by interacting with the aforementioned targets, cells, Res is thought to impede the evolution of OS. In conclusion, ferroptosis and alterations in the immunological milieu are significant factors in the development of OS, and Res may one day be employed as a therapeutic drug to treat OS.
研究领域:
肿瘤学
·
生物信息学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2026
·
IF 11
Xiaohan Chen,Peng Song,Yihao Wang,Chuanquan Wang,Liyun Ding,Xi Chen,Ning Wang
Osteosarcoma is a malignant bone tumor for which diagnosis is critical to patient prognosis. MicroRNA-588 is downregulated in osteosarcoma, highlighting its potential as a diagnostic biomarker. However, its low abundance in body fluids makes sensitive detection difficult. This study presents a label-free reflective optical fiber surface plasmon resonance (SPR) biosensor with optimized probe immobilization for ultrasensitive miRNA-588 detection in serum. The sensor utilizes plasmonic coupling between a gold film and gold nanoparticles to enhance the SPR response. By incorporating an A 15 anchor and a T 5 spacer into a single oligonucleotide, the A 15 T 5 probe promotes a more upright presentation of the recognition sequence while simplifying interface construction. Among the configurations evaluated, the A 15 T 5 probe showed the best performance for miRNA-588 detection. The biosensor exhibits a wide detection range from 10 −15 to 10 −7 M, with a low detection limit (LOD) of 1.12 × 10 −17 M, along with good stability and repeatability. In clinical sample testing, the sensor achieved an area under the receiver operating characteristic (ROC) curve of 0.95 and showed greater diagnostic discrimination than serum alkaline phosphatase in the evaluated cohort. This platform enables high-sensitivity detection of trace biomarkers, supporting the diagnosis of major diseases.
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DOI
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2021
·Vol. 25
·期 11
·4962-4973
·
IF 5.31
Mingyu He,Gege Yan,Yang Wang,Rui Gong,Hong Lei,Shuting Yu,Xiaoqi He,Guanghui Li,Weijie Du,Tianshuai Ma,Manqi Gao,Meixi Yu,Shenzhen Liu,Zihang Xu,Elina Idiiatullina,Naufal Zagidullin,Valentin Pavlov,Benzhi Cai,Ye Yuan,Lei Yang
Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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光生物学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2024
·Vol. 25
·期 8
·1-12
·
IF 3.4
Li Bo,Zhao Qianhui,Yang Hanyu,Wang Xueyuying,Zhang Zhijun,Gong Yanling,Wan Xu
Osteosarcoma (OS) is one of the most common primary bone sarcoma with high malignant degree and poor prognosis, for which there is an urgent need to develop novel therapeutic approaches. Recent research has revealed that mifamurtide significantly improved the outcome of OS patients when combined with adjuvant chemotherapy drugs including cisplatin (DDP). The present study aimed to construct a drug delivery system co-loading DDP and mifamurtide. Long-circulating targeted liposomes co-loading DDP and mifamurtide were constructed with Soy lecithin (SPC), cholesterol (Chol) and 1,2-distearoylglycero-3-phosphoethanolamine-n-[poly(ethyleneglycol)] (DSPE-PEG), modified with MMP14 targeting peptide BCY-B in the surface of liposomes. In addition to characterization, the cellular uptake, endocytosis pathway and inhibition on cell viability, migration, invasion and cell apoptosis of MG-63 cells were explored. The constructed liposomal delivery possessed the basic characteristics of liposomes and showed high affinity to MG-63 cells, resulting in high uptake efficiency in MG-63 cells. The endocytosis might be involved in multiple pathways including caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis, dependently on energy. The constructed long-circulating targeted liposomes co-loading DDP and mifamurtide significantly inhibited the cell viability, migration, invasion and cell apoptosis of MG-63 cells, improving the antitumor effect of DDP and mifamurtide in vitro . The constructed liposomal delivery system is suitable for co-loading DDP and mifamurtide to achieve active tumor targeting, supplying a new strategy for the treatment of OS. Graphical Abstract
研究领域:
药剂学
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肿瘤学
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纳米技术
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2022
·Vol. 36
·期 11
·e24698
·
IF 3.124
Chunfa Chen,Liang Liu
Background Osteosarcoma (OS) is a highly recurrent malignancy occurring among adolescents. The goal of this research was to scrutinize the role and action mechanism of KLF3-AS1 in OS. Methods Western blotting and quantitative reverse transcription real-time PCR were conducted to ascertain the mRNA expressions of miR-338-3p, KLF3-AS1, and MEF2C in OS cell lines and tissue samples. Colony formation and CCK-8 experiments were done to evaluate the proliferative capacity of the cells. Western blotting was also executed to measure the relative expressions of the proteins Bcl-2 and Bax. RNA immunoprecipitation and dual luciferase reporter experiments were carried out to validate the target relationships among MEF2C, KLF3-AS1, and miR-338-3p. Mouse xenograft models were created to assess the influences of KLF3-AS1 on the growth of tumors in vivo. Results Elevated levels of KLF3-AS1 and MEF2C and reduced amounts of miR-338-3p were identified in OS. KLF3-AS1 targeted miR-338-3p, and miR-338-3p further targeted MEF2C. Silencing KLF3-AS1 induced apoptosis and attenuated proliferation in vitro and repressed the tumor growth in vivo. Inhibiting miR-338-3p inverted the cancer-suppressing effects of KLF3-AS1 silencing. Meanwhile, loss of MEF2C partially eliminated the effects brought about by miR-338-3p downregulation, namely the stimulation of cell growth and suppression of apoptosis. Conclusions Silencing of KLF3-AS1 could repress the growth of cells and induce apoptosis by regulating miR-338-3p/MEF2C in OS. This suggests that the regulatory axis KLF3-AS1/miR-338-3p/MEF2C is a prospective target for OS treatment.
研究领域:
肿瘤学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）