JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
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2020
·Vol. 108
·期 11
·2190-2205
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IF 3.525
Yulu Yang,Bailong Tao,Yi Gong,Rui Chen,Weihu Yang,Chuanchuan Lin,Maowen Chen,Lu Qin,Yile Jia,Kaiyong Cai
After bone tumor resection, the large bony deficits are commonly reconstructed with Ti-based metallic endoprosthesis, which provide immediate stable fixation and allow early ambulation and weight bearing. However, when used in osteosarcoma resection, Ti implant-relative infection and tumor recurrence were recognized as the two critical factors for implantation failure. Hence, in this work, a novel zinc oxide nanoparticle decorating with naringin was prepared and immobilized onto Ti substrate. The drugs delivery profiles proved that in the bacterial infection and Warburg effect of osteosarcoma-induced acidic condition, naringin and Zn 2+ can be released easily from the functional Ti substrate. The anti-osteosarcoma and antibacterial assay showed the delivered naringin and Zn 2+ can induce a remarkable increase of oxidative stress in bacteria ( Escherichia coli and Staphylococcus aureus ) and osteosarcoma (Saos-2 cells) by producing reactive oxygen species (ROS). Accumulation of ROS results in damage of bacterial biofilm and bacterial membrane, leading to the leakage of bacterial RNA and DNA. Meanwhile, the increase of ROS induces osteosarcoma cell apoptosis by activating ROS/extracellular signal-regulated kinase signaling pathway. Furthermore, in vitro cellular experiments, including cell viability, alkaline phosphatase activity, collagen secretion, extracellular matrix mineralization level, indicated that the functional Ti substrate exhibited great potential for osteoblasts proliferation and differentiation. Hence, this study provides a simple and promising strategy of developing multifunctional Ti-based implants for the reconstruction of large bony after osteosarcoma resection.
研究领域:
材料科学
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生物材料
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肿瘤学
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药理学
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生物医学工程
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PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2025
·
IF 4.8
Qiang Zhang,Yu Zhang,Hui Chen,Lei-Na Sun,Bin Zhang,Dong-Sheng Yue,Chang-Li Wang,Zhen-Fa Zhang
Introduction: Elderly osteosarcoma patients often face significant postoperative challenges, including high recurrence rates and delayed wound healing. These issues are primarily due to inadequate hemostasis, reactive oxygen species (ROS)-mediated microenvironmental inhibition, and compromised bone regeneration. This study aims to address these challenges by introducing a multifunctional adhesive hydrogel designed for synergistic therapy.Methods: The hydrogel consists of carboxymethyl chitosan methacryloyl (CMCSMA) and tannic acid (TA), which form a dynamic, crosslinked polymer network capable of rapid tissue adhesion and adaptability to moist wound environments. The hydrogel incorporates ginger vesicles (GVs) loaded with doxorubicin (DOX), offering a dual therapeutic approach. The system facilitates hemostasis through physical barrier formation and activation of coagulation factors, while GVs and DOX provide controlled release for ROS scavenging, reduction of inflammation, and targeted tumor cell elimination.Results: In vitro experiments demonstrated the hydrogel’s ability to efficiently remove ROS and promote osteogenic differentiation. In a rat osteosarcoma resection model, the hydrogel significantly shortened hemostasis time compared to conventional sponges, reduced tumor recurrence, and accelerated wound healing.Discussion: This study presents a multifunctional hydrogel that combines hemostasis, antioxidation, tissue repair, and recurrence prevention. The findings suggest that this integrated therapeutic approach holds substantial potential for clinical application in elderly osteosarcoma treatment, addressing critical postoperative challenges and improving patient outcomes.
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PubMed
高影响因子
Biomaterials Advances
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2025
·
IF 6
Rongxiang Zhang,Xuelei Yin,Zenghui Xu,Qikang Yan
Purpose Development of Ce/Cu-modified black ceramics and investigation of the mechanism of anti-osteosarcoma activity. Methods Black ceramics doped with 0.3–0.7 wt% CeO 2 and CuO were prepared and analyzed using energy-dispersive X-ray spectroscopy (EDS), compression stress-strain tests, weight change, and antibacterial assays. MNNG/HOS and MG63 cells were seeded on ceramic substrates, and their adhesion and morphology were analyzed using scanning electron microscopy (SEM) and phalloidin staining. In vitro, we first assessed the anti-tumor effects of ceramic materials, then validated their impact on cuproptosis by measuring Cu 2+ levels and the expression of related proteins, including SLC31A1, HSP70, and ATP7A. Mitochondrial dysfunction and TCA abnormalities were assessed by measuring mitochondrial membrane potential, reactive oxygen species, mitochondrial structure, TCA cycle metabolites (citric acid and lactic acid), ATP levels, and DLAT and LIAS protein levels. The cuproptosis inhibitor TTM, PI3K activator 740Y P, and AKT activator SC79 were used to explore the relationship between cuproptosis and the PI3K/AKT pathway in osteosarcoma cells treated with Ce/Cu-doped black ceramics. Results Our research confirmed the superior anti-tumor properties of the Ce/Cu-modified black ceramic and its potential mechanisms against osteosarcoma. The Ce/Cu-doped black ceramic caused mitochondrial dysfunction and disrupted TCA cycle metabolism, resulting in cuproptosis in MNNG/HOS and MG63 cells. The PI3K/AKT pathway was involved in cuproptosis in osteosarcoma cells treated with Ce/Cu-modified ceramics. Conclusion Our research confirmed that Ce/Cu-modified black ceramics have superior anti-tumor effects and potential mechanisms, confirming the clinical potential of Ce/Cu-modified black ceramics in cancer treatment and providing theoretical basis for the clinical translation.
研究领域:
材料科学
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肿瘤学
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纳米医学
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细胞生物学
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生物医学工程
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高影响因子
International Journal of Biological Sciences
·
2025
·Vol. 21
·期 11
·4872-4894
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IF 10
Chen Yuxing,Tao Yong,Huang Qiu,Xu Jingtao,Wang Zhenxin,Zhang Ye,Fu Guangxu,Tan Fuqiang,Feng Keyi,Ou Yunsheng
Osteosarcoma remains a challenging malignancy with poor prognosis, particularly in metastatic cases. This study investigates the therapeutic potential and molecular mechanisms of the Hinokitiol-iron complex (Fe(hino)3) against osteosarcoma. Fe(hino)3 induced dose-dependent cell death in osteosarcoma cell lines (HOS, 143b, and K7M2) through multiple pathways. At moderate doses, Fe(hino)3 triggered ferroptosis by disrupting mitochondrial function, enhancing ROS generation and lipid peroxidation, downregulating GSS and GPX4, and upregulating HO1 and Ferritin expression. At higher doses, Fe(hino)3 activated the NLRC4/Caspase-1/GSDMD pathway, leading to pyroptosis and the release of inflammatory factors. Mechanistically, Fe(hino)3 acted as a dual-mode cell death inducer through iron overload-mediated ferroptosis and NLRC4-dependent pyroptosis while modifying the immunosuppressive tumor microenvironment. In actual clinical application, Fe(hino)3 might be used as an alternative to chemotherapy or other targeted therapies for advanced osteosarcoma at a relatively low dose to improve biosafety and reduce side effects. However, when considering it in combination with immunotherapy for advanced osteosarcoma, a relatively safe high dose is more appropriate due to the pyroptosis-mediated inflammatory response but it still needs to consider the biosafety of combination therapy. These findings provide new insights into the development of Fe(hino)3 dose-dependent therapeutic strategies for advanced osteosarcoma treatment.
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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免疫学
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生物化学
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分子生物学
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癌症研究
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高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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2022
·Vol. 41
·期 1
·1-17
·
IF 12.658
Fan Qingxin,Zuo Jing,Tian Hailong,Huang Canhua,Nice Edouard C.,Shi Zheng,Kong Qingquan
Background The high postoperative recurrence rate and refractoriness of relapsed tumors are still a conundrum for the clinical management of osteosarcoma (OS). New therapeutic options are urgently needed. Depriving the nourishment of myeloid-derived suppressor cells is a novel strategy to improve the immunosuppressive tumor microenvironment for enhanced OS therapy.Methods We synthesized a hyaluronic acid (HA)-modified metal–organic framework for combinational chemotherapy and immunotherapy of OS. Zeolitic Imidazolate Framework-8 (ZIF-8) was prepared by a one-pot synthetic method, Gemcitabine (Gem) and D-1-Methyltryptophan (D-1-MT) were loaded into the ZIF-8 during the synthesis process to make ZIF-8@Gem/D-1-MT nanoparticles (NPs). The end product (HA/ZIF-8@Gem/D-1-MT NPs) was obtained by HA modification on the surface of ZIF-8@Gem/D-1-MT NPs. The obtained HA/ZIF-8@Gem/D-1-MT NPs have excellent potential as a drug delivery vector for chemotherapy and immunotherapy in vitro and vivo.Results The results indicate that HA/ZIF-8@Gem/D-1-MT NPs were readily taken up by OS cells, and that the Gem and D-1-MT were effectively released into the acidic environment. The HA/ZIF-8@Gem/D-1-MT NPs could efficiently decrease OS cell viability (proliferation, apoptosis, cell cycle, migration and invasion). And HA/ZIF-8@Gem/D-1-MT NPs could reactivate antitumor immunity by inhibiting indoleamine 2,3 dioxygenase and myeloid-derived suppressor cells. Furthermore, animal experiments confirmed that HA/ZIF-8@Gem/D-1-MT NPs could induce intratumoral immune responses and inhibit tumor growth. Additionally, HA/ZIF-8@Gem/D-1-MT NPs have a good safety profile.Conclusion sOur findings demonstrate that the combination of Gem with D-1-MT brings new hope for the improved treatment of OS, while the generation of the nanosystem has increased the application potential and flexibility of this strategy.
研究领域:
癌症研究
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纳米技术
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药学
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免疫学
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生物医学工程
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Du Longhai,Zhu Guanghao,Xu Yanlong,Han Binxu,Wang Yu,Zhu Minhui,Meng Yingdi,Chen Huaiwen,Yu Zuochong
Introduction: The toxic side effects of systemic high-dose chemotherapy and poor sensitivity to radiotherapy hinder the survival rate of patients with osteosarcoma (OS). Nanotechnology offers new solutions for OS treatment; however, conventional nanocarriers suffer from inadequate targeting of tumors and short in vivo circulation time.Methods: Here, we designed a novel drug delivery system, [Dbait-ADM@ZIF-8]OPM, which uses OS-platelet hybrid membranes to encapsulate nanocarriers, to enhance the targeting and circulation time of nanocarriers, thereby enabling high enrichment of the nanocarriers in OS sites.Results: In the tumor microenvironment, the pH-sensitive nanocarrier, which is the metal-organic framework ZIF-8, dissociates to release radiosensitizer Dbait and the classical chemotherapeutic agent Adriamycin for the integrated treatment of OS via radiotherapy and chemotherapy. Benefiting from the excellent targeting ability of the hybrid membrane and the outstanding drug loading capacity of the nanocarrier, [Dbait-ADM@ZIF-8]OPM showed potent anti-tumor effects in tumor-bearing mice with almost no significant biotoxicity.Conclusion: Overall, this project is a successful exploration of the combination of radiotherapy and chemotherapy of OS treatment. Our findings solve the problems of the insensitivity of OS to radiotherapy and the toxic side effects of chemotherapy. Furthermore, this study is an expansion of the research of OS nanocarriers and provides new potential treatments for OS.
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高影响因子
Coatings
·
2022
·Vol. 12
·期 4
·524
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IF 3.236
Zheng Zhao,Shilu Chen,Yao Xiao,Maobin Xie,Wen Yu
After traditional osteosarcoma resection, recurrence of tumor is still a major clinical challenge. The combination of chemotherapy and photothermal therapy (PTT) has great potential in improving therapeutic effect. However, the studies using polydopamine (PDA) as photothermal transducing agent to improve the anti-cancer activity of curcumin (CM)-loaded poly (l-lactic acid) (PLLA) microparticles (PLLA/CM) have seldom been investigated. In this study, we reported the synthesis of PDA-coated PLLA/CM microparticles (PDA-PLLA/CM) prepared by PDA coating on the surface of the PLLA/CM microparticles fabricated by solution-enhanced dispersion by supercritical CO2(SEDS) for chemo-photothermal therapy of osteosarcoma. The average particle sizes of PLLA/CM and PDA-PLLA/CM microparticles with a spherical shape were (802.6 ± 8.0) nm and (942.5 ± 39.5) nm, respectively. PDA-PLLA/CM microparticles exhibited pH- and near-infrared (NIR)-responsive release behavior to promote CM release in the drug delivery system. Moreover, PDA-PLLA/CM microparticles displayed good photothermal conversion ability and photothermal stability attributed to PDA coating. Additionally, the results of in vitro anti-cancer experiment showed that 500 μg/mL PDA-PLLA/CM microparticles had good anti-cancer effect on MG-63 cells and no obvious toxicity to MC3T3-E1 cells. After incubation with PDA-PLLA/CM microparticles for 2 days, NIR irradiation treatment improved the anti-cancer activity of PDA-PLLA/CM microparticles obviously and reduced the cell viability of osteosarcoma from 47.4% to 20.6%. These results indicated that PDA-PLLA/CM microparticles possessed a synergetic chemo-photothermal therapy for osteosarcoma. Therefore, this study demonstrated that PDA-PLLA/CM microparticles may be an excellent drug delivery platform for chemo-photothermal therapy of tumors.Keywords:osteosarcoma therapy;microparticles;curcumin;synergetic chemo-photothermal therapy
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6
Xuwen Chen,Zhengli Luo,Zongjing Hu,Donghui Sun,YingYing He,Jiani Lu,Lili Chen,Shunying Liu
Chemotherapy combining with surgical treatment has been the main strategy for osteosarcoma treatment in clinical. Due to unclear pathogenesis and unidentified drug targets, significant progress has not been made in the development of targeted drugs for osteosarcoma during the past 50 years. Our previous discovery reported compound R - 8i with a high potency for the treatment of osteosarcoma by phenotypic screening. However, both the metabolic stability and bioavailability of R - 8i are poor (T 1/2 = 5.36 min, mouse liver microsome; and bioavailability in vivo F = 52.1 %, intraperitoneal administration) which limits it use for further drug development. Here, we described an extensive structure−activity relationship study of thiazolidine-4-one sulfone inhibitors from R - 8i , which led to the discovery of compound 68 . Compound 68 had a potent cellular activity with an IC 50 value of 0.217 μM, much higher half-life (T 1/2 = 73.8 min, mouse liver microsome) and an excellent pharmacokinetic profile ( in vivo bioavailability F = 115 %, intraperitoneal administration). Compound 68 also showed good antitumor effects and low toxicity in a xenograft model (44.6 % inhibition osteosarcoma growth in BALB/c mice). These results suggest that compound 68 is a potential drug candidate for the treatment of osteosarcoma.
研究领域:
肿瘤学
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药理学
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药物发现
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PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
·
IF 9.5
Tiankun Hui,Jianye Fu,Bingxin Zheng,Chenchen Fu,Baocai Zhao,Tianqi Zhang,Yifan Zhang,Chen Wang,Liangmin Yu,Yunlong Yang,Bin Yue,Meng Qiu
Two-dimensional (2D) nanomaterials as drug carriers and photosensitizers have emerged as a promising antitumor strategy. However, our understanding of 2D antitumor nanomaterials is limited to intrinsic properties or additive modification of different materials. Subtractive structural engineering of 2D nanomaterials for better antitumor efficacy is largely overlooked. Here, subtractively engineered 2D MXenes with uniformly distributed nanopores are synthesized. The nanoporous defects endowed MXene with enhanced surface plasmon resonance effect for better optical absorbance performance and strong exciton–phonon coupling for higher photothermal conversion efficiency. In addition, porous structure improves the binding ability between drug and unsaturated bonds, thus promoting drug-loading capacity and reducing uncontrolled drug release. Furthermore, the porous structure provides adhesion sites for filopodia, thereby promoting the cellular internalization of the drug. Clinically, osteosarcoma is the most common bone malignancy routinely treated with doxorubicin-based chemotherapy. There have been no significant treatment advances in the past decade. As a proof-of-concept, nanoporous MXene loaded with doxorubicin is developed for treating human osteosarcoma cells. The porous MXene platform results in a higher amount of doxorubicin-loading, faster near-infrared (NIR)-controlled doxorubicin release, higher photothermal efficacy under NIR irradiation, and increased cell adhesion and internalization. This facile method pioneers a new paradigm for enhancing 2D material functions and is attractive for tumor treatment.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Jie Cao,Chenghong Zhu,Ziqi Cao,Xue Ke
Background Chemotherapy resistance of osteosarcoma (OS) is still the crux of poor clinical curative effect.E3 ubiquitin-protein ligase Rad18 (Rad18) contributed to doxorubicin resistance in OS, which ultimately mediated DNA damage tolerance and led to a poor prognosis and chemotherapy response in patients. Methods In this study, doxorubicin was loaded in the process of Fe 2+ and siRad18 forming nanoparticles(FSD) through coordination, chitosan modified with cell penetrating peptide (H6R6) was synthesized and coated on the surface of the NPs(FSD-CHR). FSD-CHR was then dispersed in thermosensitive hydrogel(PPP) for peritumoral injection of osteosarcoma in situ. Subsequently, the physicochemical properties and molecular biological characteristics of the drug delivery system were characterized. Finally, an osteosarcoma model was established to study the anti-tumor effects of multifunctional nanoparticles and the immunotherapy effect combined with αPD-L1. Results FSD-CHR has enhanced tumor tissue permeability, siRad18 can significantly reduce Dox-mediated DNA damage tolerance and enhance anti-tumor effects, and iron-based NPs show enhanced ROS upregulation. FSD-CHR@PPP showed significant inhibition of osteosarcoma growth in vivo and a reduced incidence of lung metastasis. In addition, siRad18 was unexpectedly found to enhance Dox-mediated immunogenic cell death (ICD).FSD-CHR@PPP combined with PD-L1 blocking significantly enhanced anti-tumor effects due to decreased PD-L1 enrichment. Conclusion Hydrogel encapsulation of permeable nanoparticles provides an effective strategy for doxorubicin-resistant OS, showing that gene therapy blocking DNA damage tolerance can enhance treatment response to chemotherapy and appears to enhance the effect of ICD inducers to activate the immune system.
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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基因治疗
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免疫疗法
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PubMed
高影响因子
Journal of Functional Foods
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2022
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IF 5.223
Bo Jiang,Xinsheng Fu,Qichuan Zhang,Yunfei Du
Dioscin (DS) is a natural compound with inhibitory effects on multiple cancer types and we explored the mechanism driving the antagonizing effect of DS on osteosarcoma (OS). OS cell lines were treated with DS and microRNAs (miRs) responding to DS treatment were determined. Effects of DS on viability, apoptosis, metastasis, and miR-16-5p/HuR/Pim1 pathway activity were assessed. MiR-16-5p was inhibited before DS treatment to confirm its central role in anti-OS effects of DS. The conclusion derived from in vitro assays was verified with a mouse model. DS suppressed viability, invasion and migration, while induced apoptosis in OS cells. Moreover, the compound also induced the expression of miR-16-5p, contributing to the inhibition of HuR/Pim1 pathway. The inhibited expression of miR-16-5p counteracted the anti-OS function of DS, which was also validated in mice. Anti-OS effects of DS depended on the induction of miR-16-5p, making the compound a promising adjuvant agent for treating OS.
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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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 30
·期 4
·1907071
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IF 15.621
Shaojie Dong,Yu Chen,Luodan Yu,Kaili Lin,Xudong Wang
Chemotherapy resistance and bone defects caused by surgical excision of osteosarcoma have been formidable challenges for clinical treatment. Although recently developed nanocatalysts based on Fenton-like reactions for catalytic therapy demonstrate high potential to eliminate chemotherapeutic-insensitive tumors, insufficient concentration of intrinsic hydrogen peroxide (H 2 O 2 ) and low intratumoral penetrability hinder their applications and therapeutic efficiency. The synchronous enriching intratumor H 2 O 2 amount or nanoagents and promoting osteogenesis are intriguing strategies to solve the dilemma in osteosarcoma therapy. Herein, a multifunctional “all-in-one” biomaterial platform is constructed by co-loading calcium peroxide (CaO 2 ) and iron oxide (Fe 3 O 4 ) nanoparticles into a three-dimensional (3D) printing akermanite scaffold (AKT-Fe 3 O 4 -CaO 2 ). The loaded CaO 2 nanoparticles act as H 2 O 2 sources to achieve H 2 O 2 self-sufficient nanocatalytic osteosarcoma therapy as catalyzed by coloaded Fe 3 O 4 nanoagents, as well as provide calcium ion (Ca 2+ ) pools to enhance bone regeneration. The synergistic osteosarcoma-therapeutic effect is achieved from both magnetic hyperthermia as-enabled by Fe 3 O 4 nanoparticles under alternative magnetic fields and hyperthermia-enhanced Fenton-like nanocatalytic reaction for producing highly toxic hydroxyl radicals. Importantly, the constructed 3D AKT-Fe 3 O 4 -CaO 2 composite scaffolds are featured with favorable bone-regeneration activity, providing a worthy base and positive enlightenment for future osteosarcoma treatment with bone defects by the multifunctional biomaterial platforms.
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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再生医学
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DOI
高影响因子
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