COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
·
IF 5.999
Qinying Shi,Ying Lu,Guannan Zhang,Xin Yang,Rong Li,Guoliang Zhang,Xiudong Guo,Jianbo Song,Qin Ding
The recurrence and bone defect of malignant osteosarcoma postsurgical treatment have gained remarkable attention. Therefore, the development of multifunctional treatment platform is urgently desirable to achieve efficient tumor treatment and bone regeneration. In this paper, a multifunctional nanomaterial using mesoporous silica (MSN) as platform modified with quercetin (Qr), collagen (Col) and dopamine (PDA) was developed. Our findings demonstrated that the nanoparticles designed in this work had excellent photothermal properties and pH responsiveness. In addition, the nanoparticles had outstanding anti-tumor ability and could killed Saos-2 cells within 10 min under 808 nm laser irradiation owing to the synergistic effect of hyperthermia and Qr. Besides, the modification of PDA and Col endows the nanoparticles with excellent osteogenic activity.
研究领域:
生物医学工程
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肿瘤学
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材料科学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2016
·
IF 2.326
Zhenhua Fang,Yanpeng Sun,Hong Xiao,Peng Li,Ming Liu,Fan Ding,Wusheng Kan,Runsheng Miao
Osteosarcoma is the most common primary malignant bone tumor in the pediatric age group, and chemotherapy directed by targeted nanoparticulate drug delivery system represents a promising approach for osteosarcoma treatment recently. Here, we designed and developed a novel DOX-loaded targeted polymeric micelle self-assembled from RGD-terminated poly(ethylene glycol)- block -poly (trimethylene carbonate) (RGD-PEG-PTMC) amphiphilic biodegradable block copolymer , for high-efficiency targeted chemotherapy of osteosarcoma. Notably, the RGD-installed DOX-loaded biodegradable polymeric micelle (RGD-DOX-PM) with drug loading efficiency of 57%–73% displayed a narrow distribution (PDI = 0.05–0.12) with average sizes ranging from 46 to 73 nm depending on the DOX loading content. The release amount of DOX from RGD-DOX-PM achieved 63% within 60 h under physiological condition. Interestingly, MTT assays in MG-63 and MNNG/HOS osteosarcoma cells exhibited that half-maximal inhibitory concentration (IC 50 ) value of RGD-DOX-PM was much lower than its non-targeted counterpart (DOX-PM), implying RGD decorated nanoparticles had enhanced cell targeting ability and led to more effective anti-tumor effect. Furthermore, the targeting ability of RGD-DOX-PM was confirmed by in vitro flow cytometry and confocal laser scanning microscopy (CLSM) imaging assays, where the results showed more RGD-DOX-PM were taken up by MG-63 cells than that of DOX-PM. Therefore, this RGD decorated DOX-loaded polymeric micelle is promising for targeted chemotherapy of osteosarcoma.
研究领域:
肿瘤学
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药剂学
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生物材料学
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DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2020
·Vol. 31
·期 30
·305707
·
IF 3.551
Jiguang Tian,Ying Gu,Yonggang Li,Ting Liu
Cancer stem cells (CSCs) are considered to maintain the vitality of tumor cell populations through self-renewal and infinite proliferation, but their accessibility is still under investigation. In addition, CSCs are more resistant to chemotherapy and radiotherapy compared with common tumor cells. This study aimed to develop a kind of novel and feasible nanomaterial for targeted photothermal ablation of osteosarcoma stem cells, which could be a promising anticancer strategy. The osteosarcoma stem cells were extracted by serum-free culture and we further verified the stem cell properties. We evaluated the expression of CD271 by flow cytometry. PEGylated multifunctional hollow gold nanospheres (HGNs) were prepared based on CD271 monoclonal antibody. Bifunctional SH-PEG-COOH was used to facilitate the covalent linkage between HGNs and antibody. The efficient uptake and distribution of the functionalized HGNs were investigated using ICP-MS and TEM. Morphological studies and quantitative apoptosis evaluation were performed to detect the effect of photothermal therapy (PTT). Afterwards, we explored the possible mechanism by which PTT induced targeted killing of cancer stem cells. Osteosarcoma cells isolated from serum-free culture were detected to show stem cell properties. CD271 was found to be a potential novel surface marker for osteosarcoma stem cells. By conjugating with CD271 monoclonal antibody, these biomimetic nanoparticles can be targeted and absorbed by osteosarcoma stem cells. HGNs-PEG-CD271 achieved excellent cell viability inhibition compared with non-targeted PEGylated HGNs upon near-infrared (NIR) laser irradiation. The mechanism of targeted killing may be related to the apoptosis pathway and DNA double-strand injuries. CD271 was considered to be a surface biomarker for osteosarcoma stem cells. Functionalized HGNs based on CD271 antibody exhibited excellent potential for targeted PTT, which may be a promising strategy for osteosarcoma treatment.
研究领域:
肿瘤学
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纳米技术
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生物医学工程
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癌症干细胞
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光热治疗
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2024
·Vol. 29
·期 2
·83
·
IF 3.3
Linbang Wang,Xinyu Dou,Linzhen Xie,Xuchang Zhou,Yu Liu,Jingkun Liu,Xiaoguang Liu
Background: Lactic acid, previously regarded only as an endpoint of glycolysis, has emerged as a major regulator of tumor invasion, growth, and the tumor microenvironment. In this study, we aimed to explore the reprogramming of lactic acid metabolism relevant to osteosarcoma (OS) microenvironment by decoding the underlying lactic acid metabolic landscape of OS cells and intercellular signaling alterations. Methods: The landscape of OS metabolism was evaluated using single-cell gene expression data, lactic acid metabolism clustering, and screening of the hub genes in lactic acid metabolism of OS samples using transcriptome data. The role of the hub gene NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 6 (NDUFAF6) was validated with in vitro studies and patient experiments. Results: Single-cell RNA sequencing data validated a lactic acid metabolismhigh subcluster in OS. Further investigation of intercellular communications revealed a unique metabolic communication pattern between the lactic acid metabolismhigh subcluster and other subclusters. Next, two lactic acid metabolic reprogramming phenotypes were defined, and six lactic acid metabolism-related genes (LRGs), including the biomarker NDUFAF6, were screened in OS. In vitro studies and patient experiments confirmed that NDUFAF6 is a crucial lactic acid metabolism-associated gene in OS. Conclusions: The patterns of lactic acid metabolism in OS suggested metabolic reprogramming phenotypes relevant to the tumor microenvironment (TME) and identified NDUFAF6 as an LRG prognostic biomarker.
研究领域:
肿瘤学
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代谢生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Yiran Zhang,Qingcheng Song,Yueyao Zhang,Jiheng Xiao,Xiangtian Deng,Xin Xing,Hongzhi Hu,Yingze Zhang
Background Although systemic chemotherapy is a standard approach for osteosarcoma (OS) treatment, its efficacy is limited by the inherent or acquired resistance to apoptosis of tumor cells. Ferroptosis is considered as an effective strategy capable of stimulating alternative pathways of cancer cell demise. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy.Methods and Results A novel nanovehicle composed of arginine-glycine-aspartate (RGD) modified mesoporous silica-coated iron oxide loading Fin56 was rationally prepared (FSR-Fin56). With the RGD-mediated targeting affinity, FSR-Fin56 could achieve selective accumulation and accurate delivery of cargos into cancer cells. Upon exposure to NIR light, the nanovehicle could generate localized hyperthermia and disintegrate to liberate the therapeutic payload. The released Fin56 triggered the degradation of GPX4, while Fe3+ depleted the intracellular GSH pool, producing Fe2+ as a Fenton agent. The local rise in temperature, in conjunction with Fe2+-mediated Fenton reaction, led to a rapid and significant accumulation of ROS, culminating in LPOs and ferroptotic death. The outstanding therapeutic efficacy and safety of the nanovehicle were validated both in vitro and in vivo.Conclusion The Fin56-loaded FSR nanovehicle could effectively disturb the redox balance in cancer cells. Coupled with NIR laser irradiation, the cooperative CDT and PTT achieved a boosted ferroptosis-inducing therapy. Taken together, this study offers a compelling strategy for cancer treatment, particularly for ferroptosis-sensitive tumors like 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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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2026
·
IF 3.2
Yuru Dong,Jiaxiao Zheng,Xingtong Dong,Yixiao Lv,Zixia Xu,Chengluo Ye,Shuyuan Zhu,Haoru Dong,Yao Lv
Prolonged PFOA exposure was associated with osteosarcoma progression. • Integrated analysis revealed metabolic reprogramming and stress signatures. • Machine learning identified nine candidate hub genes. • Sub-cytotoxic PFOA enhanced proliferation and invasion of osteosarcoma cells. Perfluorooctanoic acid (PFOA), a persistent environmental pollutant, represents a chronic environmental stressor, yet its role in osteosarcoma progression remains unclear. Here, we integrated network toxicology, machine learning, immune infiltration analysis, single-cell RNA sequencing, molecular docking, molecular dynamics simulation, and in vitro assays to define the mechanisms linking long-term PFOA exposure to osteosarcoma. We identified 28 shared targets between PFOA-associated proteins and osteosarcoma-related genes, which were mainly enriched in oxidative stress, immune regulation, and metabolic reprogramming pathways. Machine learning prioritized nine candidate hub genes, including PNP, SOD2, MAT1A, RELA, PSAT1, CXCL12, PHGDH, PDK4, and CFD, with PHGDH, PSAT1, PDK4, and MAT1A suggesting a metabolism-related axis relevant to PFOA-associated osteosarcoma alterations. Single-cell and immune analyses showed distinct cell-type-specific expression patterns of these genes and their close associations with the tumor immune microenvironment. Molecular docking and molecular dynamics simulations further suggested potential structural compatibility between PFOA and several prioritized hub proteins. Experimentally, prolonged exposure to non-cytotoxic concentrations of PFOA enhanced osteosarcoma cell proliferation and invasion, whereas high concentrations were cytotoxic. Collectively, these findings suggest that long-term PFOA exposure may promote osteosarcoma progression by coupling environmental stress with metabolic reprogramming and immune dysregulation. Overview of the study design and analytical framework. PFOA, Perflurooctanoic Acid; OS, osteosarcoma; CTD, Comparative Toxicogenomics Database; DEGs, Differentially Expressed Genes; KEGG, Kyoto Encyclopedia of Genes and Genomes; AUC, Area Under the Curve; ROC, Receiver Operating Characteristic. Download: Download high-res image (278KB) Download: Download full-size image
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产品关联
DOI
PubMed
高影响因子
Anti-Cancer Agents in Medicinal Chemistry
·
2023
·Vol. 23
·期 13
·1577-1586
·
IF 2.8
Bo Yang,Bowen Wang,Guoliang Wang,Wenliang Cao,Qian Wang,Hao Pu,Wei An
Background: P-coumaric acid (p-CA) is a kind of phenylpropionic acid derived from aromatic amino acids, which is widely distributed in many plants and human diets. It has strong pharmacological and inhibitory effects on a variety of tumors. However, the role of p-CA in osteosarcoma, a tumor with a poor prognosis, is still unknown. Therefore, we aimed to evaluate the effect of p-CA on osteosarcoma and explore its potential mechanism. Objective: This study aimed to investigate whether p-CA has an inhibitory effect on the growth of osteosarcoma cells and explore its potential mechanism. Methods: MTT assay and clonogenic assay were used to detect the effect of p-CA on the proliferation of osteosarcoma cells. The effect of p-CA on apoptosis of osteosarcoma cells was detected by the Hoechst staining and flow cytometry. The effects of p-CA on the migration and invasion of osteosarcoma cells were detected by scratch healing assay and Transwell invasion assay. Western blot and PI3K/Akt pathway activator 740Y-P were used to detect the anti-tumor mechanism of p-CA on osteosarcoma cells. The effect of p-CA on osteosarcoma cells in vivo was verified by an orthotopic osteosarcoma tumor animal model in nude mice. Results: MTT assay and clonogenic assay showed that p-CA inhibited the proliferation of osteosarcoma cells. Hoechst stain and flow cytometry showed that p-CA could induce apoptosis of osteosarcoma cells and lead to G2 phase arrest of osteosarcoma cells. Transwell assay and scratch healing assay found that p-CA could inhibit the migration and invasion of osteosarcoma cells. Western blot showed that p-CA could inhibit the activity of the PI3K/Akt signaling pathway in osteosarcoma cells, and 740Y-P could reverse its inhibitory effect. In vivo mouse models, p-CA has an antitumor effect on osteosarcoma cells in vivo, and at the same time, it has less toxic side effects on mice. Conclusion: This study demonstrated that p-CA could effectively inhibit the proliferation, migration and invasion of osteosarcoma cells and promote apoptosis. p-CA may play an anti-osteosarcoma role by inhibiting PI3K/Akt signaling pathway.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Yang Yang,Hongmei Gu,Shuheng Qin,Jiajia Liu,Jianhua Xue,Yong Hu,Qiang Xue,Xianchen Liu
Background Developing nanodrugs with passive targeting capabilities that can effectively overcome the oxidative-redox homeostasis-inhibiting microenvironment of tumors offers new insights into the precise treatment of osteosarcoma.Methods CoFe2O4 nanoparticles were synthesized via the hydrothermal method and modified with polyethylene glycol 4000 on their surface, obtaining CF@P nanozymes with multi-catalytic activities similar to catalase (CAT), peroxidase (POD), oxidase (OD), and glutathione peroxidase (GPx). These nanozymes could overcome the hypoxic microenvironment and redox homeostasis in osteosarcoma treatment.Results CF@P has a size of approximately 100 nm and can stably exist under physiological conditions. It exhibits excellent photothermal effects under near-infrared II (1064 nm) laser irradiation, synergistically enhancing its catalytic activity. CF@P alleviates hypoxia by decomposing endogenous H2O2 within tumors to generate oxygen and hydroxyl radicals (·OH). Meanwhile, it consumes reduced glutathione (GSH) within tumors, inducing ferroptosis and apoptosis. CF@P exhibits low toxicity to normal cells (HUVEC) and selective killing ability against osteosarcoma cells (U2OS). In vivo, it accumulates in tumor tissues via the enhanced permeability and retention (EPR) effect, significantly inhibiting tumor growth in combination with photothermal therapy without causing significant organ toxicity, thereby prolonging the survival of tumor-bearing mice.Conclusion The CF@P nanozyme integrates the properties of multi-enzyme catalysis and photothermal therapy, disrupting the oxidative-redox homeostasis of tumor tissues, generating highly toxic hydroxyl radicals, and efficiently inducing apoptosis in osteosarcoma cells. This approach provides a new, efficient, and safe strategy for the precise treatment of hypoxic solid tumors like osteosarcoma.
研究领域:
纳米医学
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癌症治疗
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活性氧
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生物医学工程
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氧化应激
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纳米材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2021
·Vol. 44
·期 10
·1557-1564
·
IF 2.233
Yelong Ren,Yutian Lin,Jinghao Chen,Yonglong Jin
Disulfiram (DSF) chelated with copper has been confirmed to have a strong anti-tumor ability. In this study, we determined that DSF–Cu induced mitochondria-dependent apoptosis in osteosarcoma (OS), reflecting in DSF–Cu induces mitochondrial membrane potential decline, the production of reactive oxygen species (ROS), and inhibiting cells migration and invasion along with decreasing the concentration of intracellular glutathione (GSH) and facilitating the opening of mitochondrial permeability transition pore (PT) in osteosarcoma cells. These anti-tumor activities can be reversed by Cyclosporine A (CsA, PT inhibitors) and N-acetyl-L-cysteine (NAC, antioxidants). Our results suggested that DSF–Cu exerts its anti-tumor effects in OS via regulation of the ROS/Mitochondria pathway. Our findings provide the basis for DSF–Cu to treat osteosarcoma, even might develop as a potential therapy for other tumors.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Haoran Mu,Chenlu Liu,Qi Zhang,Huanliang Meng,Shimin Yu,Ke Zeng,Jing Han,Xinmeng Jin,Shi Shi,Peiyao Yu,Tianlong Li,Jing Xu,Yingqi Hua
Background: Drugs based on synthetic lethality have advantages such as inhibiting tumor growth and affecting normal tissue in vivo . However, specific targets for osteosarcoma have not been acknowledged yet. In this study, a non-targeted but controllable drug delivery system has been applied to selectively enhance synthetic lethality in osteosarcoma in vitro , using the magnetic-driven hydrogel microrobots. Methods: In this study, EPZ015666, a PRMT5 inhibitor, was selected as the synthetic lethality drug. Then, the drug was carried by hydrogel microrobots containing Fe 3 O 4 . Morphological characteristics of the microrobots were detected using electron microscopy. In vitro drug effect was detected by the CCK-8 assay kit, Western blotting, etc. Swimming of microrobots was observed by a timing microscope. Selective inhibition was verified by cultured tumors in an increasing magnetic field. Results: Genomic mutation of MTAP deletion occurred commonly in pan-cancer in the TCGA database (nearly 10.00%) and in osteosarcoma in the TARGET database (23.86%). HOS and its derivatives, 143B and HOS/MNNG, were detected by MTAP deletion according to the CCLE database and RT-PCR. EPZ015666, the PRMT5 inhibitor, could reduce the SDMA modification and inhibition of tumor growth of 143B and HOS/MNNG. The hydrogel microrobot drug delivery system was synthesized, and the drug was stained by rhodamine. The microrobots were powered actively by a magnetic field. A simulation of the selected inhibition of microrobots was performed and lower cell viability of tumor cells was detected by adding a high dose of microrobots. Conclusion: Our magnetic-driven drug delivery system could carry synthetic lethality drugs. Meanwhile, the selective inhibition of this system could be easily controlled by programming the strength of the magnetic field.
研究领域:
生物医学工程
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肿瘤学
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药理学
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材料科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2024
·
IF 4.9
Hang Wu,Lei Xie,Liang Zhu,Tengbo Yu,Yingze Zhang
As a common malignant bone tumor in adolescents, osteosarcoma (OS) possesses a very poor prognosis and lacks effective treatments. In this study, we developed a multifunctional nanotherapeutic agent (WSe 2 /AIPH/GOx) that can combine photothermal therapy (PTT) /thermodynamic therapy (TDT) /starvation therapy (ST) against OS. The prepared WSe 2 /AIPH/GOx exhibited a high photothermal conversion efficiency of 37.3% under 808 nm near-infrared laser irradiation, which could effectively eliminate tumor cells. In addition, the local high temperature caused by photothermal heat induces the rapid release and decomposition of AIPH, generating oxygen-independent alkyl radicals that promote tumor cell death in the hypoxic microenvironment. More importantly, the introduction of GOx depletes glucose to starve tumor cells on the one hand, and on the other hand can indirectly increase the thermal sensitivity of cells. In vivo experiments have demonstrated that WSe 2 /AIPH/GOx can effectively inhibit tumor growth in mice due to the combined effects of multiple therapies. Overall, this work provides an effective strategy for potential osteosarcoma treatment based on combination therapies.
研究领域:
肿瘤学
·
纳米医学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Zhang Yifei,Ning Rende,Wang Wei,Zhou Yejin,Chen Yao
Osteosarcomas commonly develop in the metaphysis of the long diaphysis, resulting in pronounced malignancy and high rates of early pulmonary metastasis. At present, osteosarcoma patients exhibit relatively poor survival rates owing these metastases and to the emergence of tumor chemoresistance. As such, there is an urgent need to identify other approaches to treating affected patients. Herein, we synthesized Fe3O4@PDA nanocomposites that exhibited excellent biocompatibility and low toxicity in human and animal model systems. The resultant nanoparticles were able to improve T2 magnetic resonance imaging and to enhance the signal-to-noise ratio associated with osteosarcoma tumors in animal models. Moreover, we were able to successfully leverage these Fe3O4@PDA particles as a photothermal agent capable of significantly inhibiting the growth of tumors and preventing their metastasis to the lung compartment. Together, these results highlight a novel therapeutic platform that has the potential to guide both the more effective diagnosis and treatment of osteosarcoma patients in clinical applications.
研究领域:
医学影像学
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肿瘤学
·
纳米医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）