CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Lan Chen,Xi Wu,Dong Li,Shaosheng Jia,Jianan Yu,Bin Li,Jingan Li,Lingchuang Bai,Shaokang Guan
Osteosarcoma is a highly malignant tumor that severely affects the physical and mental health of adolescents. Photothermal synergistic catalytic therapy is regarded as an effective and innovative strategy to eliminate tumor cells and restore bone tissue. Herein, an intelligent and anti-corrosion non-drug-loading platform, based on a dopamine-chelated iron composite coating (FeOOH/PDA-Fe), is constructed on osteogenic magnesium alloys. The prepared films function as an iron “sandwich”, which progressively enhance the corrosion resistance of Mg alloy, and pump iron ions loaded under near-infrared (NIR) irradiation and in the tumor microenvironment, but remain stable in the normal environment. Efficient photothermal therapy-driven tumor apoptosis of modified Mg alloys within the NIR window due to the strong ligand-to-metal charge transfer between intermediates of dopamine and transition metal iron oxidation. In vitro and in vivo studies reveal the synergistic mechanism of photothermal treatment on catalytic therapy for osteosarcoma of the prepared coating, and the mechanism by which the synergistic therapy re-activates the innate immune response by inducing tumor immunogenic death. The modified Mg alloys that combine effective corrosion resistance, highly efficient tumor ablation without drug resistance, and innate immune response re-activation, are likely a point-to-point solution for the comprehensive therapeutic needs of osteosarcoma.
研究领域:
材料科学
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肿瘤学
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生物医学工程
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DOI
高影响因子
MATERIALS & DESIGN
·
2024
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IF 7.6
Li-chen Ji,Jia-qing Huang,Xu-gang Zhong,Qi-hong Sun,Yong Fan,Li Yin,Qiong Zhang,Yu Cai,Zeju He
Osteosarcoma, as the most prevalent primary malignant bone tumor, has consistently shown suboptimal clinical treatment outcomes. In this manuscript, we proposed an efficacious and novel phototherapy strategy for osteosarcoma based on a photoresponsive near-infrared (NIR) material, CaCO 3 -ICG-DDP-PEG-PT (CIDP-PT), which contained calcium carbonate (CaCO 3 ) and Cisplatin (DDP) via the gas dispersion method, and indocyanine green (ICG) was encapsulated through a nanoprecipitation reaction by employing DSPE-PEG 2000 -COOH to enhance the stability and hydrophilicity. The targeting oligopeptide (PT) for osteosarcoma cells was inserted into the outer membrane of nanoparticles, thereby further enhancing the tumor-targeting capability through receptor-mediated binding. The prepared CIDP-PT nanoparticles exhibited high targeting efficiency and multifunctionality. In vitro and in vivo experiments demonstrated that CIDP-PT significantly enhanced the therapeutic efficacy for osteosarcoma via the NIR-II photoresponsive and tumor-targeting approach. It achieves efficient tumor cell eradication through multiple modalities while maintaining an exceptional level of biocompatibility. Hence, the CIDP-PT nanocarriers possess considerable practical value for future clinical applications in adjunct osteosarcoma phototherapy.
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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DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2026
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IF 19.9
Zhongming Huang,Kang Yi,Chao Fu,Guangping Zheng,Wei Zhao,Hui Hu,Yuli Yin,Rong Hu
Postoperative osteosarcoma therapy meets the substantial challenges of tumor recurrence due to incomplete eradication and functional impairment from bone defect over-resection. Herein, we establish a sonosensitizer-based therapeutic-regenerative strategy that simultaneously realizes ultrasound-triggered tumor ablation and functional bone reconstruction. By balancing intramolecular motion and intermolecular interaction, a planar skeleton/twisted rotors-structured sonosensitizer, ffBT-T, with enhanced reactive oxygen species (ROS) generation via constitutional isomerization is constructed. The rationally designed ffBT-T nanoparticles (NPs) can efficiently bind with both osteosarcoma cells and bone marrow mesenchymal stem cells (BMSCs). On the one hand, upon ultrasound activation, ROS generated by ffBT-T NPs can eliminate osteosarcoma cells in vitro through multimodal cell death (apoptosis/ferroptosis), accompanied by the successful trigger of immunogenic cell death (ICD) to prime systemic antitumor immunity. On the other hand, while eradicating tumor cells, the system shows exceptional biocompatibility with BMSCs and actively enhances their osteogenic differentiation by 2.1-fold through PI3K-Akt pathway modulation, as verified by RNA-seq and ALP/ARS assays. In vivo, this dual-function therapy successfully suppresses tumor growth and promotes bone regeneration in a clinically relevant orthotopic osteosarcoma model. This work establishes a new paradigm for “theragenerative” biomaterials by molecularly integrating tumor-specific cytotoxicity with pro-regenerative signaling, offering a clinically viable solution for postoperative cancer management.
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Xuyan Hu,Hao Zhuang,Ke Gao,Yaqi Zhu,Fan Gao,Haili Wang,Zijin Zhang,Baoqiang Su,Yubing Zhang,Cailiang Shen
Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents, featuring aggressive tumor growth and early metastasis. Current treatments, including chemotherapy and surgery, are often limited by chemoresistance and postoperative infections. Ferroptosis has emerged as a strategy to overcome chemoresistance, as it is intrinsically iron-dependent, whereas OS often exhibits dysregulated iron metabolism. Halicin, a broad-spectrum antimicrobial known to regulate iron metabolism in bacteria, was found to be a ferroptosis inducer for OS in this study. However, its therapeutic efficacy is likely hampered by rapid systemic clearance and poor tumor retention. Accordingly, we developed Halicin@Gel, an injectable hyaluronic acid hydrogel designed for localized and prolonged release. The structure, injectability, drug release behavior, biocompatibility, antibacterial activity, and antitumor efficacy of this system were characterized and evaluated in vitro and in vivo. Halicin@Gel exhibited excellent antibacterial activity and significantly inhibited OS cell proliferation and migration in vitro. Mechanistically, Halicin@Gel increased intracellular ROS levels and was associated with p38 MAPK activation, as well as ferroptosis- and apoptosis-related changes. In vivo, Halicin@Gel significantly inhibited tumor growth with minimal systemic toxicity, confirming its therapeutic potential. Thus, these findings support Halicin@Gel as a promising localized therapeutic platform with combined antitumor and antibacterial functions for OS treatment.
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Yating Lian,Junyi Zhou,Wei Li,Zhijie Yuan,Minghui Zhong,Tian Wei,Huishan Liang,Shicong Yang,Li Ding,Li-Ming Zhang,Fen Wang
Chemoresistance is the main cause of recurrence and metastasis in osteosarcoma patients; therefore, efficient therapeutic measures need to be developed to reverse chemoresistance. In this study, we designed and synthesized selenium-hybrid degradable hollow mesoporous silica nanoparticles (SeNPs) to simultaneously encapsulate doxorubicin (DOX) and carbon monoxide (CO)-releasing molecule-3 (CORM-3), and modified their surfaces with polyethylene glycol (PEG) via disulfide bonds (SeNP-PEG@DOX-CO). Subsequently, after incubation with SeNP-PEG@DOX-CO, DOX was effectively delivered into 143B cells, and CO was released in the mitochondria under the stimulation of high concentrations of glutathione (GSH) and reactive oxygen species (ROS). All in vitro anticancer functional experiments and animal experiments confirmed that DOX had CO-enhanced antitumor efficacy and that CO cooperated with chemotherapeutic drugs to resist tumors. Meanwhile, we provided for the first time a combined proteomic and metabolomic landscape of CO reversing chemotherapy resistance in osteosarcoma. This study revealed a revolutionizing osteosarcoma therapy to treat resistance for chemotherapy.
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Linbang Wang,Rui Dou,Yunlong Ma,Jiayu Zhang,Xiaomeng Cai,Jinkun Liu,Xiaoguang Liu,Jun Chen
The immunosuppressive microenvironment (TME) of osteosarcoma (OS) results in an unsatisfactory conventional therapeutic effect. Conventional chemotherapy-induced apoptosis is unsuccessful to fully activate anti-tumor immunity as it fails to release Tumor-Associated Antigens (TAAs) and promotes efferocytosis of Tumor-Associated Macrophages (TAMs). In this study, we propose to remodel TME by inducing OS cells to immunogenic cell death, including pyroptosis and necroptosis induced by efferocytosis inhibition of TAMs. Specifically, we constructed a piezoelectric catalyst, BFO@CaO₂-TPP (BCT), which targets mitochondria. Under ultrasound, BCT generated reactive oxygen species (ROS) by enhancing the Fenton reaction and released Ca 2+ to trigger mitochondrial calcium overload, which synergistically activated the caspase-3/GSDME nonclassical pyroptosis pathway and prompted the release of proinflammatory molecules from tumor cells. At the same time, BCT disrupts mitochondrial oxidative phosphorylation (OXPHOS) in TAMs, inhibits their efferocytotic capacity. More importantly, TAMs facilitate the elevation of the GSDME express and TNF/TNFR1 interaction in osteosarcoma cells, favoring pyroptosis and necroptosis. Simultaneous endogenous and exogenous regulation is ultimately transforms the ‘cold’ TME into a ‘hot’ state. Patient-derived organoid-based validation confirmed the translational potential of this strategy.
研究领域:
肿瘤学
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免疫学
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纳米医学
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分子生物学
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转化医学
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生物材料学
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产品关联
DOI
高影响因子
TALANTA
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2025
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IF 6.1
Ying Jin,Junjie Zhang,Xinyi Wu,Cheng Qu,Xingru Fang,Yi Yang,Yue Yuan,Honglin Liu,Zhenzhen Han
Osteosarcoma (OS) calls for early diagnosis to significantly improve patient survival rates. Exosomes hold significant potential as noninvasive biomarkers for the early diagnosis of cancer. Here, we design a microfluidic device to purify and analyze plasma-derived exosomes by label-free surface-enhanced Raman spectroscopy (SERS) profiling for OS diagnosis. Exosomes were isolated, purified, and enriched using a size-dependent microfluidic chip with tangential flow filtration, achieving a high recovery rate of 82 %. The isolated exosomes were then analyzed by label-free SERS using a nanoarray chip with self-assembly monolayers of gold nanoparticles (GNPs). Exosomes originating from different OS cell types were differentiated based on the intrinsic SERS signals. Our approach was further employed to analyze the plasma-derived exosomes from healthy donors and OS patients without the need for specific biomarker labeling. A machine learning-based diagnostic model for OS was constructed, achieving an accuracy of 93 %. The findings indicate that our method is valuable for noninvasive and precise diagnosis of OS and could be generalized to other diseases in the future.
研究领域:
生物医学工程
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癌症诊断
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纳米技术
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Yangyun Wang,Yanxian Wu,Liubing Li,Chunjie Ma,Shaodian Zhang,Subin Lin,Leshuai W. Zhang,Yong Wang,Mingyuan Gao
How to effectively treat malignant osteosarcoma remains clinically challenging. Programmed delivery of chemotherapeutic agents and immunostimulants may offer a universal strategy for killing osteosarcoma cells while simultaneously eliciting in situ antitumor immunity. However, targeted chemoimmunotherapy lacks a reliable delivery system. To address this issue, we herein developed a bioinspired calcium phosphonate nanoagent that was synthesized by chemical reactions between Ca2+ and phosphonate residue from zoledronic acid using bovine serum albumin as a scaffold. In addition, methotrexate combination with a phosphorothioate CpG immunomodulator was also loaded for pH-responsive delivery to enable synergistic chemoimmunotherapy of osteosarcoma. The calcium phosphonate nanoagents were found to effectively accumulate in osteosarcoma for nearly 1 week, which is favorable for exerting the vaccination effects in situ by maturing dendritic cells and priming CD8+ T cells to suppress the osteosarcoma progression and pulmonary metastasis through controlled release of the three loaded agents in the acidic tumor microenvironment. The current study may thus offer a reliable delivery platform for achieving targeted chemotherapy-induced in situ antitumor immunity.
研究领域:
肿瘤学
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纳米医学
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免疫疗法
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
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IF 10.2
Jianan Yu,Shaosheng Jia,Rongbang Sun,Tong Zhang,Xinyuan Cai,Manli Song,Lan Chen,Han Lin,Shaokang Guan
Frequent tumor recurrence and postoperative bacterial infections after osteosarcoma surgery have increased the demand for advanced bone implants. Although magnesium and its alloys are considered promising candidates for next-generation bone implants, their clinical application remains limited due to inadequate corrosion resistance. In this work, manganese oxide (MnO x ) nano-coatings with varying Mn 3+ /Mn 2+ ratios were fabricated on the surface of ZE21C alloys via heat treatment, effectively enhancing corrosion resistance. The MnO x nano-coatings consisted of multiple semiconductors with different Mn 3+ /Mn 2+ ratios, and Mn 2 O 3 with a narrower band gap became the dominant phase with heat treatment, resulting in a significant improvement in the photothermal conversion performance. In vivo and in vitro experiments demonstrated that samples with higher Mn 3+ /Mn 2+ ratios disrupted redox homeostasis, inducing lipid peroxidation of biological membranes. Additionally, valence electrons in the semiconductors could be excited by NIR irradiation to generate photogenerated carriers, forming transmembrane electron-transfer channels with adhered tumor and bacterial cells, leading to structural membrane disruption and sustained antibacterial and tumor cell ablation. Furthermore, Mg alloys modified with MnO x nano-coatings exhibited excellent biocompatibility and did not inhibit mitochondrial function of normal cells. This work provides a broader range of options and practical solutions for developing intelligent bone tissue-engineering materials for postoperative osteosarcoma.
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Bowen Duan,Hongting Liu,Xiaoxuan Ji,Jingwen Dong,Xinping Luo,Feiran Zhang,Minjie Sun,Zhanwei Zhou
Osteosarcoma is one of the commonest malignant bone tumors in children and adolescents, and its preferred treatment is chemotherapy. However, the lack of sufficient blood vessels in the bone tissue and the dense collagen fibers in osteosarcoma severely weaken the drug-directional accumulation effect and intra-tumoral penetration, leading to poor therapeutic efficacy. Herein, we reported a bone-targeted permeable nanomicelle (Co1-PTX@DSAA) composed of aspartic acid (Asp)-modified dextran (DSAA) to deliver paclitaxel (PTX) and collagenase 1 (Co1) simultaneously for highly effective osteosarcoma treatment. The prepared nanomicelle possessed excellent osteosarcoma targeting ability as Asp can combine with hydroxyapatite (HAP) in bone. More intelligently, the surface-absorbed Co1 endowed PTX@DSAA with a special function like a nano-icebreaker, which could quickly destroy the collagen fibers to promote PTX penetration deeply in the tumor. Our work suggests that Co1-PTX@DSAA nanomicelles could quickly combine with HAP and Ca 2+ at an adsorption rate of ∼ 60% and ∼ 32%, respectively. Meanwhile, the penetration depth of Co1-PTX@DSAA could even reach 70 μm in the multicellular spheroids (MCSs) model. The tumor treatment efficiency of Co1-PTX@DSAA is 1.51 times that of free PTX. Overall, this unprecedented nanomicelle can simultaneously facilitate drug accumulation and deep penetration in the tumor, which will provide a promising strategy for future safe and high-efficiency clinical osteosarcoma treatment.
研究领域:
肿瘤学
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药学
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纳米技术
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
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IF 9.229
Wentao Dang,Ke Yi,Enguo Ju,Yuanyuan Jin,Yanteng Xu,Haixia Wang,Wei-Chih Chen,Kun Wang,Yu Wang,Yu Tao,Mingqiang Li
The postoperative tumor recurrence and chemotherapy resistance in clinical osteosarcoma treatment have raised an imperative need to develop local implants for selectively killing residual tumor cells and simultaneously provide a scaffold for effectively filling the tumor resection-induced bone defects. Herein, a multifunctional platform is developed through successively coating TiN microparticles and doxorubicin (DOX) on the surface of tricalcium phosphate (TCP) scaffolds to achieve synergetic effects of photothermal therapy and chemotherapy for osteosarcoma. The content of TiN and DOX in the scaffolds can be flexibly adjusted by immersing the scaffolds into the solution containing different concentrations of TiN and DOX. The excellent therapeutic effect was achieved both in vitro and in vivo through the precise photothermal therapy and localized controlled-release chemotherapy. Moreover, the overall bulk scaffolds provide the mechanical support for bone tissue when implanting scaffolds into bone defects resulting from surgical removal of osteosarcoma. Importantly, using the poly(d,l-lactide) (PDLLA) as the medium, the scaffolds can be exploited as a universal platform for loading different kinds of therapeutic agents. This study may provide insights into designing multifunctional local implantation for eradicating tumors after surgical interventions with mitigated side effects.
研究领域:
生物医学工程
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癌症研究
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材料科学
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组织工程
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
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IF 8.387
Zi-Fei Zhou,Tuan-Wei Sun,Feng Chen,Dong-Qing Zuo,Hong-Sheng Wang,Ying-Qi Hua,Zheng-Dong Cai,Jun Tan
Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering . Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo ; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis. The as-prepared CPPA hybrid microspheres are promising in anti-osteosarcoma and bone regeneration , which simultaneously display excellent properties on drug delivery and osteogenic differentiation of hBMSCs.
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DOI
PubMed
高影响因子
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