ACS Omega
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2026
·
IF 5.2
Zhiyu Chen,Junhong Chen,Shuang Liu,Xu Zhou,Yichuan Zhang,Yunsheng Jiang,Xiao Liu,Yuan Zhang,Xiangling Pu,Hui Zhang
Osteosarcoma is the most prevalent primary bone cancer affecting children and adolescents, characterized by its high invasiveness and the challenges in treatment posed by multidrug resistance. Cancer stem cells significantly contribute to poor clinical outcomes; however, current targeted therapies remain limited in their effectiveness. In this study, we developed a novel dual-responsive nanomedicine designed to target the microenvironment of osteosarcoma cancer stem cells (OCSCs) and osteosarcoma itself, which selectively releases all-trans retinoic acid and paclitaxel, termed mPCDAP. Our findings indicate that mPCDAP rapidly releases all-trans retinoic acid to suppress stemness under conditions of elevated glutathione, subsequently increasing intracellular reactive oxygen species levels in tumor cells. This mechanism further facilitates the release of paclitaxel under conditions of highly reactive oxygen species, thereby inducing apoptosis in osteosarcoma cells. Additionally, mPCDAP was effectively internalized by both osteosarcoma cells and OCSCs, with in vitro and in vivo results demonstrating significant synergistic antitumor effects, promoting apoptosis and markedly reducing tumor stemness. This study presents a novel approach and promising prospects for targeted therapy of osteosarcoma and OCSCs.
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
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2026
·
IF 4
Zhewen Deng,Mengyuan Zhang,Senqiang Zhu,Yunlong Zhang,Haitao Liao,Jiaqi Li,Peiyu Yan,Qi Zhang,Rui Liu,Bo Ma
Osteosarcoma (OS), a highly aggressive bone cancer with a dismal prognosis in the metastatic setting, urgently demands novel therapeutic modalities. While phototherapy offers a promising, minimally invasive strategy, its clinical efficacy is often hampered by the poor aqueous solubility of photosensitizers and the development of multidrug resistance. In response, we constructed the dual-modal nanoplatform BDP-NPs by leveraging a multifunctional F127/TPGS mixed micelle to encapsulate a cationic BODIPY photosensitizer, thereby creating a system engineered for enhanced tumor accumulation and to overcome multidrug resistance. Benefiting from their uniform size, colloidal stability, and hypoxia-responsive properties, the BDP-NPs demonstrate potent reactive oxygen species generation and high photothermal conversion efficiency under 525 nm laser irradiation. This dual-modal action induces severe mitochondrial dysfunction, thereby triggering apoptosis in both 3D tumor spheroids and tumor tissues. The synergistic phototherapy elicited profound mitochondrial-targeted cytotoxicity, inhibited clonogenic survival, and significantly suppressed tumor growth in human osteosarcoma models, all while maintaining a favorable biosafety profile. Mechanistic analyses revealed that this synergistic phototherapy plays a pivotal role in suppressing the YAP1/β-catenin axis, thereby reversing the epithelial-mesenchymal transition (EMT) program and consequently inhibiting OS cell proliferation, migration and invasion. This study not only establishes BDP-NPs as a potent and biocompatible nanotherapeutic for OS but also presents a groundbreaking phototherapeutic strategy to disrupt the YAP1/β-catenin axis-a key signaling network driving tumorigenesis and malignant progression. This approach provides a robust conceptual foundation for devising next-generation phototherapeutics that precisely target oncogenic signaling in aggressive cancers.
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BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Jianping Hu,Jinhu Chen,Caili Zhao,Pei Yu,Wenjun Xu,Yong Yin,Lei Yang,Zhenzhen Zhang,Lingyi Kong,Chao Zhang
Osteosarcoma, the most prevalent malignant bone tumor in adolescents, is characterized by its aggressiveness and tendency to metastasize. Despite the advancements in treatment that have improved survival rates for localized cases, metastatic osteosarcoma remains challenging to treat due to the limited efficacy of current therapies and the severe side effects of chemotherapy. Epithelial-mesenchymal transition (EMT) is a key factor in osteosarcoma metastasis, and the miR-194/215 cluster, which is upregulated in osteosarcoma, promotes this process. This study sought to investigate natural compounds that could counteract the miR-194/215 cluster’s effects and inhibit osteosarcoma metastasis. By analyzing miRNA databases and clinical data, a signature gene set for the miR-194/215 cluster was established, and the LINCS database was screened to find natural compounds with antagonistic effects. Icariside II, an active component of Epimedium, was identified as a potential inhibitor and was shown to reduce the migration and invasion of osteosarcoma cells in vitro and lung metastasis in vivo . The study utilized various techniques, including Gene Set Enrichment Analysis (GSEA), Drug Affinity Responsive Target Stability (DARTS), Cellular Thermal Shift Assay (CETSA), molecular docking, and enzyme activity assays, to identify phosphoglycerate kinase 1 (PGK1) as the target protein of Icariside II. It was found that Icariside II competitively inhibits PGK1 by binding to its ADP binding pocket, reducing its activity and thus antagonizing the miR-194/215 cluster’s promotion of EMT in metastatic osteosarcoma. The results suggest that Icariside II could be a promising therapeutic agent for metastatic osteosarcoma, providing new targets and strategies for clinical treatment.
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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天然产物化学
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Journal of Magnesium and Alloys
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2026
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IF 13.8
Dong Li,Tong Zhang,Shaosheng Jia,Jianan Yu,Rongbang Sun,Bin Yin,Liguo Wang,Lingchuang Bai,Lan Chen,Shaokang Guan
Osteosarcoma (OS) poses a severe threat to human health, and the standard clinical treatment involves prosthetic replacement after surgical removal combined with radiotherapy and chemotherapy. However, the recurrence of residual tumors and extensive bone defects leads to a poor prognosis for patients. Zoledronic acid (ZA) is clinically used for tumor treatment and osteoclast inhibition. Nevertheless, intravenous infusion of ZA has poor targeting and significant toxicity to normal tissues. Biodegradable Mg alloys have excellent mechanical and biological compatibility, making them ideal for orthopedic implants. However, their application is limited due to poor corrosion resistance. This work applied a multi-composite layered double hydroxide (LDH)-ZA/PDA coating to the surface of ZE21C alloy. The composite coating adsorbed ZA in weakly alkaline or neutral conditions and released ZA under near-infrared (NIR) irradiation in the tumor microenvironment (TME). The stimuli-responsive release of ZA was confirmed to be related to the NIR-TME-triggered change in LDH interlayer spacing. In vitro and in vivo experiments showed that this multi-composite coating improved corrosion resistance, responded to TME and NIR stimuli to release ZA and reactive oxygen species, effectively targeting and killing tumor cells and osteoclasts through the AKT/GSK-3β signaling pathway. It also transformed OS from “cold tumors” into “hot tumors”, reactivated macrophage-mediated tumor immunity, and promoted osteogenesis. The chemo-thermal-therapeutic approach of the composite coating achieves a “three-birds-with-one-stone” effect. This study offers new insights into applying Mg alloys in prosthetic replacements after OS surgery.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2022
·Vol. 45
·期 12
·1733-1742
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IF 2.264
Yongbin Jing,Mingkun Jia,Jinpeng Zhuang,Dong Han,Changlong Zhou,Jinglong Yan
Osteosarcoma (OS) is the most common primary malignant bone tumor and is mainly diagnosed in children. Toll-like receptor 9 (TLR9) is expressed in various tumor cells and was correlated with cancer progression. However, the underlying mechanism of TLR9 on the OS progression remains unclear. Our previous study demonstrated that the expression of TLR9 was positively correlated with the development stage of OS. Herein, we further evaluated the actual roles and the molecular mechanism of TLR9 on regulating OS cell proliferation and metastasis. Our data showed that TLR9 was upregulated in OS cells compared to normal osteoblastic cells, and knockdown of TLR9 inhibited OS cell proliferation and induced cell cycle arrest by the decreased expression of cyclin D1, CDK2, and p-Rb, while TLR9 overexpression exerted the inverse effects. Furthermore, TLR9 overexpression could enhance the migration and invasion activities of the OS cells by the upregulation of matrix metalloproteinases 2 (MMP2) and MMP9, and the opposite result was observed in TLR9-silenced cells. Moreover, the nuclear factor kappa B (NF-κB) signaling pathway was activated by TLR9, and TLR9-induced malignant phenotype of OS cells was abrogated by the NF-κB antagonist BAY11-7082. Our study indicated that TLR9 might play a critical role in facilitating OS progression by activating the NF-κB signaling pathway, which may provide a valuable therapeutic target for OS.
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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癌症研究
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BIOMATERIALS
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2022
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IF 15.304
Yu-Xiang Ge,Tai-Wei Zhang,Lei Zhou,Wang Ding,Hai-Feng Liang,Zhi-Chao Hu,Qin Chen,Jian Dong,Feng-Feng Xue,Xiao-Fan Yin,Li-Bo Jiang
Poor immunogenicity and compromised T cell infiltration impede the application of immune-checkpoint blockade (ICB) immunotherapy for osteosarcoma (OS). Although autophagy is involved in enhancing the immune response, the synergistic role of autophagy in ICB immunotherapy and the accurate control of autophagy levels in OS remain elusive and challenging. Here, we designed a pH-sensitive autophagy-controlling nanocarrier, [email protected] @PEG-FA (CBZP), loading a natural derivative, curcumin (CUR), to boost the immunotherapeutic response of PD-1/PD-L1 blockade by activating immunogenic cell death (ICD) via autophagic cell death, and BMS1166 to inhibit the PD-1/PD-L1 interaction simultaneously, enhancing the tumor immunogenicity and sensitizing the antitumor T cell immunity. After entering tumor cells, the pH-sensitive nanoparticles induced autophagy and decreased the intracellular pH , which in turn further facilitated the release of CUR to enhance autophagic activity. Transferring CBZP to orthotopic OS tumor-bearing mice showed powerful antitumor effects and established long-term immunity against tumor recurrence, accompanied by enhanced dendritic cell maturation and tumor infiltration of CD8 + T lymphocytes. Collectively, CBZP exhibited synergistic effects in treating OS by combining ICD induction with checkpoint blockade, thereby shedding light on the use of autophagy control as a potential clinical therapy for OS.
研究领域:
肿瘤学
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免疫疗法
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纳米技术
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药理学
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CARBON
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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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Bioactive Materials
·
2023
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IF 18.9
Hao Huang,Lei Qiang,Minjie Fan,Yihao Liu,Anchun Yang,Dongbiao Chang,Jinsheng Li,Tong Sun,Yiwei Wang,Ruoyi Guo,Hanjie Zhuang,Xiangyu Li,Tailin Guo,Jinwu Wang,Huan Tan,Pengfei Zheng,Jie Weng
The resection of malignant osteosarcoma often results in large segmental bone defects, and the residual cells can facilitate recurrence. Consequently, the treatment of osteosarcoma is a major challenge in clinical practice. The ideal goal of treatment for osteosarcoma is to eliminate it thoroughly, and repair the resultant bone defects as well as avoid bacterial infections. Herein, we fabricated a selenium/strontium/zinc-doped hydroxyapatite (Se/Sr/Zn-HA) powder by hydrothermal method, and then employed it with polycaprolactone (PCL) as ink to construct composite scaffolds through 3D printing, and finally introduced them in bone defect repair induced by malignant osteosarcoma. The resultant composite scaffolds integrated multiple functions involving anti-tumor, osteogenic, and antibacterial potentials, mainly attributed to the anti-tumor effects of SeO 3 2− , osteogenic effects of Sr 2+ and Zn 2+ , and antibacterial effects of SeO 3 2− and Zn 2+ . In vitro studies confirmed that Se/Sr/Zn-HA leaching solution could induce apoptosis of osteosarcoma cells, differentiation of MSCs, and proliferation of MC3T3-E1 while showing excellent antibacterial properties. In vivo tests demonstrated that Se/Sr/Zn-HA could significantly suppress tumors after 8 days of injection, and the Se/Sr/Zn-HA-PCLs scaffold repaired femoral defects effectively after 3 months of implantation. Summarily, the Se/Sr/Zn-HA-PCLs composite scaffolds developed in this study were effective for tumor treatment, bone defect repair, and post-operative anti-infection, which provided a great potential to be a facile therapeutic material for osteosarcoma resection.
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Journal of Orthopaedic Translation
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2022
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IF 4.889
Feng-wei Zhang,Li-yang Peng,Chuan-Jian Shi,Jian-chi Li,Feng-xiang Pang,Wei-ming Fu,Xiao-hua Pan,Jin-fang Zhang
Background Osteosarcoma (OS) is a common type of malignant bone tumor in adolescents with high risk of metastasis. However, the clinical management still remains unsatisfactory. Traditional Chinese medicine (TCM) has been widely considered as an alternative treatment, and their extracts have proved to possess great potential for drug discovery. Baicalein (BA), the active pharmaceutical ingredient of rhizoma coptidis , was proved to have anti-tumor properties in OS, but the mechanism remains poorly understood. Methods The potential anti-cancer effects on cell growth, cell cycle, apoptosis and migration were examined in OS cells. Moreover, the lncRNA-Neighboring Enhancer of FOXA2 (lncRNA-NEF) and Wnt/β-catenin signaling were detected by qPCR and Western blotting assays. The in vivo effect of GA on tumor growth was investigated using a xenograft mice model. Results In the present study, BA was found to significantly suppress tumor growth in vitro and in vivo. And it was also found to inhibit the invasion and metastasis as well. As for the mechanism investigation, lncRNA-NEF was obviously upregulated by BA in OS cells, and thus induced the inactivation of Wnt/β-catenin signaling. Moreover, lncRNA-NEF knockdown partially reversed the BA-induced anti-cancer activities; and successfully compensated the suppressive effect on Wnt/β-catenin signaling. We therefore suggested that BA induced the inactivation of Wnt/β-catenin signaling through promoting lncRNA-NEF expression. Conclusions In conclude, our results demonstrated that BA suppressed tumor growth and metastasis in vitro and in vivo through an lncRNA-NEF driven Wnt/β-catenin regulatory axis, in which lncRNA-NEF was upregulated by BA, and thus induced the inactivation of Wnt/β-catenin signaling. The Translational potential of this article The findings derived from this study validates the anti-cancer activity of BA in OS and provides a novel underlying mechanism, which suggest that BA may be a potential candidate to develop the effective drug for OS patients.
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FASEB JOURNAL
·
2023
·Vol. 37
·期 5
·e22924
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IF 4.8
Liangjie Lu,Huihan Wang,Minjie Yang,Lijun Wang,Kaifeng Gan
Beta-tricalcium phosphate (β-TCP) is considered as one of the most promising biomaterials for bone reconstruction. This study generated a functional molybdenum disulfide (MoS 2 )/polydopamine (PDA)/−bone morphogenetic protein 2 (BMP2)-insulin-like growth factor-1 (IGF-1) coating on the β-TCP scaffold and analyzed the outcomes. The MoS 2 /PDA-BMP2-IGF-1@β-TCP (MPBI@β-TCP) scaffold was prepared by 3D printing and physical adsorption, followed by characterization to validate its successful construction. The in vitro osteogenic effect of the MPBI@β-TCP scaffold was evaluated. It was found that MPBI@β-TCP augmented the adhesion, diffusion and proliferation of mesenchymal stem cells (MSCs). The alkaline phosphatase (ALP) activity, collagen secretion and extracellular matrix (ECM) mineralization along with the expression of Runx2, ALP and OCN were also enhanced in the presence of MPBI@β-TCP. Additionally, MPBI@β-TCP stimulated endothelial cells to secrete VEGF and promoted capillary-like tubule formation. We then confirmed the biocompatibility of MPBI@β-TCP to macrophages and its anti-inflammatory effects. Furthermore, under near-infrared (NIR) laser irradiation, MPBI@β-TCP produced photothermal effect to not only kill MG-63 osteosarcoma cells, but also enhance bone regeneration in vivo with biosafety. Overall, this work demonstrates that 3D-printed MPBI@β-TCP with enhanced osteogenic activity under NIR laser irradiation has a vast potential in the field of tissue defects.
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PROCESS BIOCHEMISTRY
·
2023
·
IF 4.4
Ziping Ma,Chunyang Fang
The significant adverse effects and chemoresistance accompanying single-agent chemotherapy reduce its therapeutic effectiveness. The synergistic treatment of osteosarcoma with chemotherapy and photothermal therapy (PTT) has attracted much interest recently due to the improved therapeutic effectiveness of anticancer drugs. In this research, we engineered a new 5-fluorouracil (5FU) by modifying ZIF-8 nanocomposites with polydopamine (PD) and loading them with the drugs. Here, modifying PD prevented the drug's explosive release, enhanced the nanocomposites' biocompatibility, and rendered it more successful at absorbing near-infrared (NIR) light. Excellent photothermal effects were also seen when the PD/5FU@ZIF-8 NCs were exposed to NIR light and employed as a drug-targeted delivery device. In vitro biological tests showed that PD/5FU@ZIF-8 NCs effectively lowered mitochondrial membrane potentials (MMPs) in 143B cells, resulting in death; the addition of photothermal properties improved the anticancer impact and reduced the chemotherapeutic drug dose. In addition, the optimized PD/5FU@ZIF-8 NCs (30 μg/mL) demonstrated enhanced photothermal transformation capability and aided the killing of tumor cells. These findings definitively demonstrate that PD/5FU@ZIF-8 NCs have an additive impact on chemo-photothermal therapy and remarkable biocompatibility; these results have strong potential for preclinical translation for osteosarcoma and other cancer cells.
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Advanced Healthcare Materials
·
2024
·
IF 10
Kaiyuan Liu,Pengfei Zan,Zihua Li,Hengli Lu,Peng Liu,Li Zhang,Hongsheng Wang,Xiaojun Ma,Feng Chen,Jing Zhao,Wei Sun
The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here we present a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable systemic antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study offers a comprehensive approach to treat OS by mild photothermal therapy and modulating the immune microenvironment, exhibiting considerable potential in addressing the constraints associated with current therapeutic modalities. This article is protected by copyright. All rights reserved
研究领域:
癌症治疗
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免疫学
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纳米技术
·
肿瘤学
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