CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Wentao Dang,Yuanyuan Jin,Ke Yi,Enguo Ju,Chenya Zhuo,Hongyan Wei,Xingqiao Wen,Yu Wang,Mingqiang Li,Yu Tao
Simultaneously eliminating tumor cells and filling the bone defects after tumor resection is still highly challenging for clinical bone tumor treatment. Three-dimensional (3D) printing technology , which provides scaffolds with patient-specific accurate geometry and desirable feature, has gained great attention for supplying a promising candidate for therapy of bone tumors. In this work, we constructed multifunctional scaffolds by coating hemin and doxorubicin (DOX) on the strut surface of 3D-printed bioactive glass ceramics (BGC-HM-DOX). Owing to the surficial hemin particles, BGC-HM-DOX scaffolds showed excellent photothermal response under near-infrared laser irradiation. Besides, BGC-HM-DOX scaffolds could effectively kill osteosarcoma cells in vitro and suppress tumor growth in vivo via the combination of photothermal therapy and chemotherapy. Therefore, this scaffold may provide a high clinical potential for precision medicine in tumor-induced bone defect management.
研究领域:
生物医学工程
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癌症治疗
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材料科学
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骨科手术
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2020
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IF 5.115
Lingling Ou,Haiyingjie Lin,Yuwei Song,Guoqiang Tan,Xiujuan Gui,Jinyuan Li,Xiaoting Chen,Zhendong Deng,Shaoqiang Lin
Background Gene therapy is considered a novel way to treat osteosarcoma, and microRNAs are potential therapeutic targets for osteosarcoma. miR-214 has been found to promote osteosarcoma aggression and metastasis. Graphene oxide (GO) is widely used for gene delivery for the distinct physiochemical properties and minimal cytotoxicity. Methods Polyethyleneimine (PEI)-functionalized GO complex was well-prepared and loaded with miR-214 inhibitor at different concentrations. The load efficacy was tested by gel retardation assay and the cy3-labeled fluorescence of cellular uptake. The experiments of wound healing, immunofluorescence staining, Western blot, qRT-PCR and immunohistochemical staining were performed to measure the inhibitory effect of the miR-214 inhibitor systematically released from the complexes against MG63, U2OS cells and xenograft tumors. Results The systematic mechanistic elucidation of the efficient delivery of the miR-214 inhibitor by GO-PEI indicated that the inhibition of cellular miR-214 caused a decrease in osteosarcoma cell invasion and migration and an increase in apoptosis by targeting phosphatase and tensin homolog (PTEN). The synergistic combination of the GO-PEI-miR-214 inhibitor and CDDP chemotherapy showed significant cell death. In a xenograft mouse model, the GO-PEI-miR-214 inhibitor significantly inhibited tumor volume growth. Conclusion This study indicates the potential of functionalized GO-PEI as a vehicle for miRNA inhibitor delivery to treat osteosarcoma with low toxicity and miR-214 can be a good target for osteosarcoma therapy.
研究领域:
肿瘤学
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分子生物学
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纳米技术
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药学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2024
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IF 3.8
Tao Yining,Li Leike,Yang Xiyu,Yin Shiyu,Zhang Zhanxiang,Wang Haoyu,Pu Ruochen,Wang Zongyi,Zhang Qi,Mu Haoran,Wu Chenqiong,He Jin,Yang Liu
The advancements in the field of micro-robots for drug delivery systems have garnered considerable attention. In contrast to traditional drug delivery systems, which are dependent on blood circulation to reach their target, these engineered micro/nano robots possess the unique ability to navigate autonomously, thereby enabling the delivery of drugs to otherwise inaccessible regions. Precise drug delivery systems can improve the effectiveness and safety of synthetic lethality strategies, which are used for targeted therapy of solid tumors. MYC-overexpressing tumors show sensitivity to CDK1 inhibition. This study delves into the potential of Ro-3306 loaded magnetic-driven hydrogel micro-robots in the treatment of MYC-dependent osteosarcoma. Ro-3306, a specific inhibitor of CDK1, has been demonstrated to suppress tumor growth across various types of cancer. We have designed and fabricated this micro-robot, capable of delivering Ro-3306 precisely to tumor cells under the influence of a magnetic field, and evaluated its chemosensitizing effects, thereby augmenting the therapeutic efficacy and introducing a novel possibility for osteosarcoma treatment. The clinical translation of this method necessitates further investigation and validation. In summary, the Ro-3306-loaded magnetic-driven hydrogel micro-robots present a novel strategy for enhancing the chemosensitivity of MYC-dependent osteosarcoma, paving the way for new possibilities in future clinical applications.
研究领域:
生物医学工程
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肿瘤学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Haoyu Wang,Haitian Jiang,Yining Tao,Binghui Yang,Jiakang Shen,Haoran Mu,Chongren Wang,Xiyu Yang,Zhengdong Cai,Mu Li,Wei Sun,Liu Yang,Mengxiong Sun
Introduction: Osteosarcoma, characterized by high mortality and disability rates, poses a significant challenge due to its complex genetic background and the absence of specific membrane receptors, which hinder effective targeted therapy. Active targeting has emerged as a promising approach to address this issue.Methods: In this study, magnetically driven hydrogel robots (MMHR) were utilized to load and deliver drugs precisely to target sites. The drugs included SCR1481B16, a specific MET inhibitor proven to inhibit MET-driven tumor growth, and Anlotinib. The microrobots were designed to navigate under magnetic guidance, enhancing drug efficacy while minimizing damage to normal tissues.Results: The study explored the potential of MMHR loaded with SCR1481B16 and Anlotinib in the treatment of Anlotinib-resistant osteosarcoma. The microrobots were successfully designed and produced, demonstrating the ability to deliver drugs precisely to tumor sites. Evaluation of the microrobots showed an enhanced sensitivity of tumors to Anlotinib, providing new insights into the treatment of drug-resistant osteosarcoma.Discussion: Tumors overexpressing MET often develop resistance to VEGFR-targeted drugs. The use of SCR1481B16 as a MET inhibitor in combination with Anlotinib, delivered by magnetically driven hydrogel microrobots, offers a novel strategy to overcome this resistance. However, further in-depth research and validation are required before the clinical application of this method can be considered.Conclusion: In conclusion, magnetically driven hydrogel microrobots loaded with SCR1481B16 provide a promising new strategy for enhancing the sensitivity of Anlotinib-resistant osteosarcoma, bringing hope for future clinical applications in the treatment of this challenging disease.
研究领域:
肿瘤学
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生物医学工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Zhaolong Yu,Ziqi Gan,Wei Wu,Xiaojiang Sun,Xiaofei Cheng,Chen Chen,Bihui Cao,Zhongyi Sun,Jiwei Tian
Osteosarcoma, a predominant malignant tumor among adolescents, exhibits high mortality and suboptimal immunotherapy efficacy due to a collagen-dense extracellular matrix (ECM) that hinders cytotoxic T lymphocyte (CTL) infiltration. Herein, we developed mesoporous polydopamine (MPDA) nanoparticles encapsulating bromelain and the immune adjuvant R848 (M@B/R), aimed at enhancing photothermal immunotherapy. These nanoparticles efficiently accumulate at the tumor site following injection. Upon near-infrared (NIR) light irradiation, photothermal therapy (PTT) induces immunogenic cell death in tumor cells and, with the aid of R848, efficiently promotes dendritic cell maturation, activating antitumor immunity and leading to CTL infiltration into the tumor. Concurrently, NIR-induced heating activates bromelain, resulting in ECM degradation and improved CTL penetration into the tumor. Our in vivo evaluations demonstrate potent antitumor effects in osteosarcoma-bearing mice. This integrated approach offers a promising strategy for overcoming physical barriers in ECM-rich tumors, marking a significant advancement in the treatment of osteosarcoma.
研究领域:
肿瘤学
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免疫学
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Sheng Xu,Ziwei Hu,Weihao Zheng,Chaozhen Qin,Xiaoyu Bai,Qinghua Yang,Tao Zeng,Dandan Mo,Bo Zhou,Chun Lu,Xiaomin Chen,Biying Tan,Jinmin Zhao,Li Zheng
Osteosarcoma (OS), a highly malignant primary tumor, poses significant threats. Chemotherapy remains the main treatment approach but is limited by low drug bioavailability, poor permeability, and notable side effects. Herein, a near-infrared light (NIR)-driven and GSH-responsive poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP) nanomotor, wherein disulfide bonds served as GSH sponsors and platinum nanoparticles as producers of reactive oxygen species (ROS) to induce cell apoptosis, combined with NIR-driven propulsion to enhance the inhibitory effect of encapsulated doxorubicin (DOX). The results demonstrated that the PSPDP nanomotor can be effectively driven due to its good photothermal properties, with its movement speed increased 2.10 times under NIR laser exposure. Additionally, the efficiency of DOX release increased with the increase in GSH concentration, demonstrating favorable GSH responsiveness. Pt-NPs also exhibited good photothermal properties, enabling self-thermophoresis to drive. Minimal cytotoxic effects of PSPDP were observed on a series of cell lines compared with DOX solution and Pt-NPs. Notably, the Pt-NPs generated a significant amount of ROS, synergistically enhancing the therapeutic effect of DOX, as evidenced by a 5.53-fold increase in OS cell growth inhibition and evident osteosarcoma growth inhibition in the nude mice model. Thus, the NIR-driven, localized, and low-toxic nanomotor may offer a promising therapeutic strategy for OS intervention. Statement of significance Enhancing drug penetration efficiency and developing delivery systems that respond to the tumor microenvironment to release drugs are effective strategies for treating osteosarcoma (OS). Here, a near-infrared (NIR) light-driven and glutathione (GSH)-responsive nanomotor, integrating poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP), was produced and used for OS treatment. This PSPDP nanomotor exhibits significant advancements in photothermal activation and self-thermophoresis, enabling a 2.10-fold increase in movement speed under NIR exposure. Such enhanced motility improves the localized delivery and controlled release of doxorubicin, thus increasing drug bioavailability and minimizing systemic toxicity. Additionally, the nanomotor's ability to generate reactive oxygen species significantly amplifies its therapeutic impact, evidenced by a remarkable 5.53-fold increase in tumor growth inhibition. These features make the PSPDP nanomotor a promising candidate for effective and targeted OS treatment strategies.
研究领域:
肿瘤学
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纳米医学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2026
·Vol. 45
·期 1
·103
·
IF 14.3
Bai Guannan,Zhang Lin,Zhao Manli,Zhang Jingyao,Chen Wenhao
Background Osteosarcoma (OS) is an aggressive bone malignancy in adolescents, with poor prognosis and limited survival improvement over decades, necessitating new therapeutic targets. Prior research identified Leucyl-tRNA synthetase (LARS) as critical for OS proliferation, prompting this investigation into its underlying mechanisms. Method Utilizing clinical OS samples, we assessed LARS and primase p58 subunit 2 (PRIM2) expression via immunohistochemistry. In vitro studies employed OS cell lines for LARS/PRIM2 overexpression or knockdown, followed by functional assays: MTT, colony formation, EdU staining, Transwell migration/invasion, and flow cytometry for cell cycle/ROS/Ca 2 ⁺ analysis. Xenograft models were used to evaluate tumor progression in vivo . Multi-omics analyses included transcriptome sequencing, proteomic profiling, and telomeric repeat amplification protocol-PCR to assess translational regulation. Stable isotope labeling by amino acids in cell culture (SILAC) determined leucine-dependent PRIM2 synthesis. Mechanisms were further probed using inhibitors and rescue experiments. Results LARS expression is significantly elevated in OS, and its overexpression enhances proliferation but inhibits invasion and migration in vitro and in vivo . Conversely, LARS silencing in OS cells results in cell cycle arrest. Mechanistically, the upregulation of LARS in OS is associated with increased glycolysis and DNA replication and a reduction in endoplasmic reticulum stress, while elevating the oncogene PRIM2 through leucine-dependent translational control. Conclusion Our findings highlight the crucial oncogenic role of the LARS/PRIM2 axis in promoting the pathogenesis of OS, primarily through the alleviation of endoplasmic reticulum stress and the activation of translation processes.
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2025
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IF 4.8
Dapeng Li,Yuanfan Li,Jie Cang,Xianwen Yan,Feipeng Wu,Xuan Sun,Wenchao Zhang
Introduction: Osteosarcoma (OS) is the most common primary malignant bone tumor in pediatric populations. Its treatment is complicated by chemotherapy-induced toxicity and limited induction of immunogenic cell death (ICD).Methods: To address these challenges, we developed a pH-responsive, multi-component nanoparticle system designed to co-deliver doxorubicin (DOX), monophosphoryl lipid A (MPLA), and a PD-1/PD-L1-targeting peptide, integrated with the immune-modulating polymer PEG-PC7A. The system was optimized using both one-factor-at-a-time (OFAT) and Box-Behnken design (BBD).Results: The optimized nanoparticles had a hydrodynamic size of 110 nm, high encapsulation efficiency (97.15%), and pH-sensitive drug release (91% at pH 6.5). In vitro studies showed enhanced ICD markers, including calreticulin exposure and ATP/HMGB1 release, aswell as synergistic dendritic cell maturation via dual STING/TLR4 pathway activation. In an orthotopic LM8 osteosarcoma model, the nanoparticles significantly suppressed tumor growth, promoted cytotoxic T lymphocyte infiltration, reduced regulatory T cells, and established long-term immune memory.Discussion: The combination of ICD induction, innate immune activation, and checkpoint blockade reprogrammed the tumor microenvironment, amplifying anti-tumor immune responses. These results demonstrate the potential of this multifunctional nanoparticle platform as an effective immunochemotherapeutic strategy for osteosarcoma, offering enhanced therapeutic efficacy and reduced systemic toxicity.
研究领域:
肿瘤学
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免疫学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Shouwen Su,Wei-Chih Chen,Wentao Dang,Quanmin Wang,Manyi Su,Haixia Wang,Yu Tao,Kun Wang,Enguo Ju
Surgical resection combined with adjuvant chemotherapy represents the primary therapeutic strategy for osteosarcoma, yet significant challenges remain in preventing postoperative tumor recurrence and drug resistance. Herein, an engineered sandwich-structured hydrogel scaffold (sandwich/MTO-CuHCF) loading copper hexacyanoferrate nanoparticles (CuHCF) and mitoxantrone (MTO) with multimodal therapy was developed by using in situ stacked 3D-printing technology. The sandwich architecture provided distinct compartmentalization of therapeutic agents, thereby mitigating the risk of physicochemical incompatibility. Upon implantation of the sandwich/MTO-CuHCF scaffold at the tumor resection site, CuHCF and MTO were sequentially and sustainably released. On one hand, CuHCF depleted intracellular glutathione and catalyzed a Fenton-like reaction to generate cytotoxic hydroxyl radicals, leading to effective cancer cell killing. On the other hand, the subsequently released MTO, an anthracycline chemotherapeutic agent, induced DNA damage in tumor cells. Notably, the excellent photothermal conversion efficiency of sandwich/MTO-CuHCF under near-infrared irradiation not only enhanced the Fenton-like reaction through localized hyperthermia but also facilitated photothermal ablation of osteosarcoma cells. Remarkably, in a mouse osteosarcoma resection model, scaffold implantation significantly inhibited tumor recurrence. Our study provides a conceptual framework for the development of implantable scaffolds to achieve effective suppression of postoperative tumor recurrence.
研究领域:
生物医学工程
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纳米医学
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肿瘤学
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材料科学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Smart Medicine
·
2025
·Vol. 4
·期 3
·e70013
·
IF 11.6
Haiwen Su,Yuanhai Chen,Zhiyan Xuan,Haoyu Ren,Peihua Lu,Miaoqing Zhao,Huan Wang
Pharmacological chemotherapy remains a cornerstone in treating osteosarcoma (OS), where the application of drug combinations not only enhances therapeutic efficacy but also mitigates adverse side effects. However, the absence of an efficient and reliable drug screening platform poses a significant challenge in optimizing these combination therapies. In this study, we introduce a novel OS chip designed to facilitate the high-throughput and precise evaluation of drug combination efficacy, addressing this critical gap in OS treatment research. Leveraging the precise control of microfluidic electrospray technology, we successfully fabricated core–shell microcarriers (CSMs) encapsulating OS cells with uniform size and monodisperse distribution. Through three-dimensional culture, OS cell spheroids were efficiently formed within the CSMs, which were subsequently integrated into a microfluidic chip equipped with a concentration gradient generator and cell culture chambers. This innovative platform enables high-throughput screening of single drugs and diverse drug combinations. Our results demonstrate that this OS-on-a-chip exhibits significant potential for clinical drug screening, offering a robust tool for optimizing therapeutic strategies in OS treatment. Summary Innovative osteosarcoma-on-a-chip for high-throughput drug screening Core–shell microcarriers enable uniform 3D OS spheroid formation Microfluidic electrospray technology for precise drug combination testing Concentration gradient generator enhances multi-drug efficacy evaluation
研究领域:
生物医学工程
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药理学
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微流控技术
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癌症研究
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Guannan Zhang,Zhuangzhuang Wu,Yongqiang Yang,Jing Shi,Jia Lv,Yi Fang,Zhen Shen,Zhi Lv,Pengcui Li,Xiaohong Yao,Weiyi Chen,Xiaochun Wei,Paul K. Chu,Xiangyu Zhang
After prosthesis replacement for the treatment of bone tumors, incomplete removal of tumor cells is the main challenge. Moreover, combating implant-associated infection and simultaneously promoting osseointegration are highly demanded for orthopedic implants and therefore, a multifunctional coating that produces tumor therapeutic effects, antibacterial activity, and osteogenesis at the same time is of clinical significance. Herein, a phototherapy platform composed of rare-earth elements - doped titanium dioxide nano-shovel/quercetin/L-arginine (TiO 2 @UCN/Qr/LA) on titanium bone implant is fabricated. The stable nano-shovel structure prepared by a hydrothermal method improves the photothermal conversion ability of titanium. Incorporation of Yb and Er enhances the upconversion capability, thereby facilitating generation of reactive oxygen species (ROS) during exposure to near-infrared II (NIR-II) light. Furthermore, under the action of ROS, L-arginine is catalyzed to release nitric oxide (NO) free radicals. In vitro and in vivo experiments indicate that the combined actions of ROS, quercetin, and NO not only inhibit bone tumor growth at a temperature of 48 ℃, but also eliminate Staphylococcus aureus biofilms on the Ti implants at a mild temperature of 45 ℃ upon illumination with a 1,060 nm laser. Moreover, TiO 2 @UCN/Qr/LA promotes angiogenesis and osteogenic differentiation, reduces inflammation, and accelerates formation of new bone tissues.
研究领域:
生物材料
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生物医学工程
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癌症治疗
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骨科
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光热疗法
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抗菌技术
✓ 已验证
产品关联
DOI
高影响因子
Oncology Letters
·
2017
·Vol. 15
·期 1
·879-884
·
IF 1.39
Qian Liu,Bo Xu,Wanshan Zhou
The correlation between PAK5 (P21-activated kinase 5) and Ezrin gene expression and chemotherapy resistance of osteosarcoma patients was investigated. The cisplatin (CDDP)-resistance model of osteosarcoma cells SOSP-9607/CDDP was established to detect the cell growth curve. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the drug resistance of cells to chemotherapy drugs. Transwell assay was used to detect the invasive capacity of cells. Semi-quantitative PCR (qPCR) was used to detect the mRNA expression levels in the drug resistance-related genes PAK5 and Ezrin. Western blot analysis was used to detect the protein expression levels in PAK5 and Ezrin. Tumor tissues were taken from the osteosarcoma patients with chemotherapy resistance to detect the expression levels of PAK5 and Ezrin via immunohistochemical detection, and the correlation between PAK5 and Ezrin expressions was studied. The results of MTT assay showed that the growth rate of SOSP-9607 was similar to that of SOSP-9607/CDDP, and the difference was not statistically significant (P>0.05). The sensitivity of SOSP-9607 to CDDP was significantly higher than that of SOSP-9607/CDDP, and the difference was statistically significant (P<0.01). Transwell assay showed that the migration capacity of SOSP‑9607/CDDP was significantly better than that of SOSP-9607 (P<0.01), indicating that the drug resistance cell lines of osteosarcoma were constructed successfully. Semi-qPCR and western blot analysis showed that the protein expression levels in PAK5 and Ezrin in SOSP-9607/CDDP were significantly higher than those in SOSP-9607 (P<0.01). The results of immunohistochemistry showed that the expression quantities of PAK5 and Ezrin in osteosarcoma tissues were significantly higher than those in para-tumor tissues (P<0.01). Pearson's correlation analysis showed that expression of PAK5 and Ezrin was positively correlated (r=0.197, P=0.023). The osteosarcoma resistance is closely related to the expression levels of PAK5 and Ezrin genes. Thus, PAK5 and Ezrin genes may affect the tolerance of osteosarcoma patients to chemotherapy drugs during treatment via the synergistic effect.
研究领域:
肿瘤学
·
分子生物学
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细胞生物学
✓ 已验证
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）