INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Min Cheng,Yi Jiang,Ying Wang,Yilun Wu,Yishen Zhu
Chemotherapy in osteosarcoma treatment has long been stagnating, leaving challenges in the treatment of patients with metastatic and recurrent osteosarcoma. Modulation of macrophages in the tumour microenvironment offers great opportunities to elicit a durable antitumour effect. Here, we employed aluminium hydroxide nanosheets (nAl) to co-deliver the chemotherapy drug doxorubicin (DOX) and immune modulator zoledronic acid (ZA). The hexagon nAl was obtained by a facile approach, with a high positive surface charge for the loading of ZA. With 37% and 8.5% payloads to ZA and DOX, the formed nAl/ZD showed efficient cell growth inhibition to LM8 osteosarcoma cells, and preferential M1 polarization induction to RAW 264.7 macrophage cells. Furthermore, enhanced antitumour effect was observed with nAl/ZD-enabled macrophage activation in the LM8/RAW 264.7 co-culture model. Our results may inspire new treatment strategies for osteosarcoma.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Bone Oncology
·
2021
·
IF 4.072
Zhaoan Lu,Chuanwen Wang,Xiaolong Lv,Wen Dai
Background Circular RNAs (circRNAs) are a class of endogenous RNAs that are involved in osteosarcoma progression. Hsa_circ_0010220 (circ_0010220) is a circRNA generated by gene Rho Guanine Nucleotide Exchange Factor 10 Like (ARHGEF10L) and is upregulated in osteosarcoma, but its functional role in osteosarcoma is limited studied. This study aimed to illustrate the regulatory mechanism underlying circ_0010220 in osteosarcoma. Methods 51 paired tumor and normal tissues were obtained from osteosarcoma patients. circ_0010220, microRNA (miR)-198 and Syntaxin 6 (STX6) abundances were examined by quantitative reverse transcription polymerase chain reaction and western blot. Cell proliferation, cell cycle, apoptosis, migration and invasion were analyzed via Cell Counting Kits-8 (CCK-8), colony formation, flow cytometry and transwell analyses. Target relationship was verified via dual-luciferase reporter analysis, RNA immunoprecipitation and pull-down. The in vivo function was analyzed using a xenograft model. Results Circ_0010220 was elevated in osteosarcoma tissues and cells, and was related to the lower survival rate of osteosarcoma patients. Circ_0010220 knockdown inhibited cell proliferation, migration and invasion, but induced cell cycle arrest and apoptosis in vitro . Besides, circ_0010220 silence curbed the growth of xenograft osteosarcoma tumors in vivo . Mechanistic research revealed that miR-198 is a target of circ_0010220, and directly targets STX6. Moreover, circ_0010220 upregulated the expression of STX6 by sponging miR-198 to regulate cell proliferation, migration, invasion, cell cycle, and apoptosis. Conclusion Circ_0010220 contributes to osteosarcoma progression through mediating miR-198/STX6 axis, which might be a novel therapeutic target for osteosarcoma therapy.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Fengtian Zhang,Jiaoting Chen,Weihong Luo,Changlong Wen,Wei Mao,Yutian Yang,Chunting Liu,Youjia Xu,Weiliang Chen,Lijuan Wen
Clinical treatment for osteosarcoma (OS) is still lacking effective means, and no significant progress in OS treatment have been made in recent years. Single chemotherapy has serious side effects and can produce drug resistance easily, resulting poor therapeutic effect. As a modern and non-invasive treatment form, photodynamic therapy (PDT) is widely used to treat diverse cancers. Chemotherapy in combination with PDT is a particularly efficient antitumor method that could overcome the defects of monotherapies. Since mitochondria is a key subcellular organelle involved in cell apoptosis regulation, targeting tumor cells mitochondria for drug delivery has become an important entry point for anti-tumor therapy. Herein, we rationally designed a core-shell structured biomimetic nanoplatform, i.e., D@SLNP@OSM-IR780, to achieve tumor homologous targeting and mitochondria targeted drug release for chemotherapy combined with PDT against OS. Upon 808 nm laser irradiation, D@SLNP@OSM-IR780 exhibited excellent photo-cytotoxicity in vitro . The excellent targeting effect of D@SLNP@OSM-IR780 in tumor tissues produced a tumor inhibition rate of 98.9% in vivo . We further indicated that synergistic chemo-photodynamic effect induced by D@SLNP@OSM-IR780 could activate mitochondria-mediated apoptosis pathway, along with host immune response and potential photothermal effect. On the whole, D@SLNP@OSM-IR780 is revealed to be a promising platform for OS targeted combination therapeutics.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-23
·
IF 14.7
Zhang Hanchen,Montesdeoca Nicolás,Tang Dongsheng,Liang Ganghao,Cui Minhui,Xu Chun,Servos Lisa-Marie,Bing Tiejun,Papadopoulos Zisis,Shen Meifang,Xiao Haihua,Yu Yingjie,Karges Johannes
The majority of anticancer agents have a reduced or even complete loss of a therapeutic effect within hypoxic tumors. To overcome this limitation, research efforts have been devoted to the development of therapeutic agents with biological mechanisms of action that are independent of the oxygen concentration. Here we show the design, synthesis, and biological evaluation of the incorporation of a ruthenium (Ru) catalyst into polymeric nanoreactors for hypoxic anticancer therapy. The nanoreactors can catalyze the oxidation of glutathione (GSH) to glutathione disulfide (GSSG) in hypoxic cancer cells. This initiates the buildup of reactive oxygen species (ROS) and lipid peroxides, leading to the demise of cancer cells. It also stimulates the overexpression of the transient receptor potential melastatin 2 (TRPM2) ion channels, triggering macrophage activation, leading to a systemic immune response. Upon intravenous injection, the nanoreactors can systemically activate the immune system, and nearly fully eradicate an aggressive osteosarcoma tumor inside a mouse model.
研究领域:
肿瘤学
·
生物化学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Yu Zhang,Man Shu,Xiao Chu,Jielong Zhou,Qiao Zhou,Guoqing Zhong,Renshan Li,Yue He,Guiquan Zhang,Ziyang Xu,Teliang Lu,Mei Li,Xiongfa Ji,Anjun Qin,Jin Ke,Zhidan Tan
Osteosarcoma (OS) is an aggressive malignant tumor with high recurrence and metastatic potential, primarily affecting adolescents. Despite the standard clinical "sandwich" treatment regimen, patient survival rates have remained stagnant. Microwave ablation (MWA), known for its rapid heating and strong tissue penetration, has emerged as a viable therapeutic strategy for bone tumors. However, MWA poses challenges, particularly the potential for iatrogenic damage to adjacent healthy tissues and the concern that inappropriate energy delivery parameters may paradoxically stimulate neoplastic progression. In this study, microwave-triggered organic nanoparticles, termed ATT, were synthesized via a spontaneous [2+2] cycloaddition-cycloreversion (CA-CR) reaction. Findings from cell-based assays and animal studies indicated that ATT effectively generated reactive oxygen species (ROS) and produced heat under microwave (MW) irradiation, achieving a remarkable tumor inhibition rate of 95%. Owing to its unique donor-acceptor (D-A) structure and twisted molecular configuration, ATT facilitates efficient charge transfer under MW irradiation. The process generates electron-hole pairs, enhancing ROS production and enabling effective microwave dynamic therapy (MDT) effect. Moreover, ATT acts as a polar molecule that efficiently absorbs MW and generates heat through resonance, thereby potentiating the therapeutic performance of microwave thermal therapy (MTT). This study presents a novel microwave-triggered organic nanomaterial that integrates MTT and MDT, offering a prospective therapeutic intervention for OS.
研究领域:
肿瘤学
·
纳米医学
·
生物有机化学
·
治疗放射学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials
·
2026
·Vol. 19
·期 8
·1504
·
IF 3.7
Deju Gao,Yuhan Du,Junjie Deng,Zhengxin Gan,Wei Zhang,Yuxiao Lai,Yuanchi Zhang
Treatment of postsurgical osteosarcoma remains one of the major challenges in orthopedic clinics. Conventional implants often fail to address complex pathological issues, including irregular bone defects, residual tumor cells, and delayed bone regeneration. Herein, this study reports a multifunctional shape-memory polyurethane (SMPU)/manganese dioxide (MnO2) composite that provides adaptive support, antitumor activity, and osteogenic bioactivity. SMPU was synthesized by introducing 1,4-butanediol (BDO) and dimethylolpropionic acid (DMPA) as chain extenders at a specific ratio. Commercial MnO2nanoparticles were incorporated as both a photothermal agent and a bioactive component to achieve multifunctionality. As designed, a coordination system was formed between the polymer chains and MnO2nanoparticles within the composites. The influence of MnO2content was systematically investigated. Although increasing MnO2amounts improved photothermal and mechanical performance, excessive incorporation adversely affected the molecular structure and compromised the composite’s biocompatibility. By adjusting the MnO2content, the composites were demonstrated to possess robust mechanical performance, good shape-memory behavior, and controllable Mn2+release. Additionally, the composites exhibited tunable photothermal performance under near-infrared (NIR) irradiation. Furthermore, in vitro studies confirmed that the composites containing 4 wt% MnO2could eliminate tumor cells via photothermal effects and promote the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Overall, the SMPU/MnO2composites had superior multifunction for treating irregular bone defects following bone tumor surgery.
✓ 已验证
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2021
·Vol. 53
·期 7
·903-911
·
IF 3.848
Zhao Jing,Li Peifeng,Zhu Hua,Ge Fengqin,Liu Jie,Xia Jingjun,Hang Pengzhou
Recent studies suggest that 7,8-dihydroxyflavone (7,8-DHF) inhibits the development of several tumors. However, its role in osteosarcoma (OS) remains unknown. This study was designed to investigate the effects and underlying mechanisms of 7,8-DHF that may influence OS development. Human OS cell lines (U2OS and 143B) were treated with 7,8-DHF; cell viability and cell migration were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and wound-healing assay, respectively; and cell death and apoptosis were evaluated by LIVE/DEAD staining and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, respectively. Reactive oxygen species production was measured using 2,7-dichlorodihydrofluorescein diacetate probe. Akt, Bcl-xL/Bcl-2 asociated death promoter (Bad), p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK) expression and their respective phosphorylation levels were detected by western blot analysis. We found that 7,8-DHF reduced cell viability in a dose-dependent manner and also promoted apoptosis, inhibited migration, and induced oxidative stress in OS cells. Moreover, 7,8-DHF inhibited Akt, Bad, and p38MAPK, but activated ERK and JNK signals. In summary, our results suggest that 7,8-DHF inhibits OS progression, possibly by regulating Akt/Bad and MAPK signaling. These findings provide new evidence for the pharmacological effects of 7,8-DHF that may improve drug therapy for OS patients.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Cairong Li,Wei Zhang,Ruiqi Wang,Xiang-Fu Du,Dongchun Jiang,Ben Liu,Yangyi Nie,Jiaxin Liao,Yingqi Chen,Xingjie Liang,Ling Qin,Yuxiao Lai
Osteosarcoma (OS) is the most prevalent primary malignancy of bone. Inhibition of OS recurrence and subsequent bone formation after surgery remains a challenge for decades. Innovative biomaterials with the dual function of tumor therapy and bone regeneration have emerged as a promising strategy for OS treatment. We developed a bioactive nanoparticle (MDA-NPs) composed of magnesium oxide nanoparticle (M-NPs) core and 2-Aminoethyl methacrylate (2-AM) grafted polydopamine (PDAM) shell. The phosphonate modified methacrylamide chitosan (CMP) and polyacrylamide (PAM) were prepared to form a pre-gel, and then a series of MDA-NPs nanocomposite with 0 mg/mL, 0.5 mg/mL, 2.5 mg/mL, 5 mg/mL, and 10 mg/mL were incorporated and coded as [email protected] , 0.5NP/ [email protected] , 2.5NP/ [email protected] , 5NP/ [email protected] , 10NP/ [email protected] , respectively. We found that 5NP/ [email protected] hydrogel showed a balanced photothermal effect, mechanical property, and osteogenesis for MDA-NPs can be used as a co-crosslinker, photothermal agent, and Mg 2+ reservoir. Human OS cells (143B) could be efficiently inhibited by 5NP/ [email protected] hydrogel with near-infrared (NIR) laser irradiation, achieving complete suppression of tumor recurrence in vitro and in vivo . The released Mg 2+ efficiently promotes the osteogenic activities of mouse embryo osteoblast precursor cells (MC3T3-E1) and 5NP/ [email protected] hydrogels exhibit highly effective bone repair performance in a critical cranial defect rat model. In conclusion, the 5NP/ [email protected] hydrogel demonstrated excellent dual functions of suppressing OS recurrence and repairing bone defects. This novel multifunctional bioactive hydrogel provides an encouraging idea of synergistic postoperative treatment of OS.
研究领域:
生物材料学
·
肿瘤学
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Jia-Xin Cai,Ji-Hua Liu,Jun-Yong Wu,Yong-Jiang Li,Xiao-Han Qiu,Wen-Jie Xu,Ping Xu,Da-Xiong Xiang
Purpose In order to prepare a biomimetic nano-carrier which has inflammatory chemotaxis, homologous targeting and reduce immune clearance, for targeted chemotherapy of osteosarcoma, we fabricated the paclitaxel-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with 143B-RAW hybrid membrane (PTX-PLGA@[143B-RAW] NPs) and evaluate its anti-cancer efficacy in vitro and vivo.Methods PTX-PLGA@[143B-RAW] NPs were prepared by the ultrasonic method and were characterized by size, zeta potential, polymer dispersion index (PDI), Coomassie bright blue staining, transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC). Cellular uptake, cell viability assay, flow cytometry and chemotactic effect of PTX-PLGA@[143B-RAW] NPs were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy and safety of PTX-PLGA@[143B-RAW] NPs were evaluated in 143B osteosarcoma xenograft mice.Results The hybrid membrane successfully coated onto the surface of PLGA nanoparticles. PTX-PLGA@[143B-RAW] NPs had a drug loading capacity of 4.24 ± 0.02% and showed targeting ability to osteosarcoma. PTX-PLGA@[143B-RAW] NPs showed high cellular uptake and improved anti-cancer efficacy against 143B cells. More importantly, PTX-PLGA@[143B-RAW] NPs treatment suppressed tumor growth in tumor-bearing mice with minimal damage to normal tissues.Conclusion PTX-PLGA@[143B-RAW] NPs could be used for targeted drug delivery and osteosarcoma therapy.
研究领域:
纳米技术
·
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Ming Gong,Yufeng Huang,Huixiong Feng,Jiaming Lin,Anfei Huang,Jinxin Hu,Qinglian Tang,Xiaojun Zhu,Shisong Han,Jinchang Lu,Jin Wang
Treatments for osteosarcoma (OS) with pulmonary metastases reach a bottleneck with a survival rate of 10–20%. The suppressive tumor associated macrophages(TAMs) and CD47 over-expression greatly lead to the treatment failure. Sonodynamic therapy (SDT) can generate ROS with deep tumor penetration to induce tumor cell apoptosis , which is reported to further induce M1 macrophage polarization. CD47 inhibition combined with SDT to synergistically modulate TAMs may induce superior effects for OS treatment. In this work, for the first time, a biomimetic nanodrug named MPIRx was deveploped by loading IR780 (a sonosensitizer) and RRx-001 (a CD47 inhibitor) in PEG-PCL nanomicelles and then coating with OS cell membranes . After ultrasound activation, the nanodrug significantly inhibited OS proliferation and migration, induced apoptosis and immunogenic cell death in OS cells. Furthermore, MPIRx could guide macrophage migrating towards tumor cells and promote M1-type polarization while increasing the phagocytosis activity of macrophages on OS cells. Ultimately, MPIRx showed good tumor accumulation in vivo and successfully inhibited subcutaneous OS and orthotopic tumor with deterioration of pulmonary metastasis. Overall, by creating a local oxidative microenvironment and modulating the TAMs/CD47 in tumor tissue, the MPIRx nanodrug presents a novel strategy for macrophage-related immunotherapy to successfully eliminate OS and inhibit the intractable pulmonary metastasis.
研究领域:
肿瘤学
·
药学
·
免疫治疗
·
纳米技术
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2024
·
IF 3.5
Shuang Shen,Shuli Nong,Xianpeng Zhang,Jiaqi Song,Caiting Meng,Xinling Liu,Liang Shao,Guanying Li,Li Xu
Poor cellular permeability greatly hampers the utilization of anionic Ir(III) complexes, though efficiently emissive and remarkably stable, in cell-based diagnosis. To overcome this barrier, we present the development of an alkaline phosphatase (ALP)-responsive, anionic, and aggregation-induced emission (AIE)-active Ir(III) complex (Ir1) for specific recognition of osteosarcoma cells. Containing phosphate moieties, Ir1 exhibits a net −1 charge, enabling charge repulsion from the cell membrane and resulting in low cellular uptake and good biocompatibility in normal osteoblast cells. Upon ALP-mediated hydrolysis of phosphate groups, the resulting dephosphorylated product, Ir2, demonstrates a positive charge and increased lipophilicity, promoting cellular uptake and activating its AIE properties for specific recognition of osteosarcoma cells that express elevated levels of ALP. This study elucidates the role of ALP as an ideal trigger for enhancing the cellular permeability of phosphate ester-containing Ir(III) complexes, thus expanding the potential of anionic Ir(III) complexes for biomedical applications.
研究领域:
癌症生物学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jianxu Zhou,Taotao Huo,Junxian Miu,Ziyi Wang,Xiaoyu Shan,Jiaqi Song,Yuquan Bai,Shuichu Hao,Chun Zhang,Shichang Liu,Biao Wang,Guanying Li
The inhibition of residual tumor recurrence while repairing bone defects poses a challenging issue for postoperative osteosarcoma treatment. Here, we develop a self-assembling peptide hydrogel (GelA) for the targeted delivery of cisplatin (CDDP), aiming to integrate postoperative tumor inhibition with bone defect repair. GelA exhibits exceptional biocompatibility, high loading capacity for CDDP, and superior bone adhesion. After in situ injection to bone defects, CDDP-loaded hydrogel GelA-CDDP demonstrates a strong affinity for hydroxyapatite, thereby facilitating optimal bone adhesion and prolonging the retention time of CDDP in a postoperative wound. Furthermore, GelA-CDDP can regulate the distribution and release behavior of CDDP, minimizing off-target effects and optimizing the therapeutic outcomes of chemotherapy and osteogenesis. Finally, in the orthotopic osteosarcoma transplantation model in mice, postoperative treatment with GelA-CDDP significantly inhibits residual osteosarcoma recurrence as well as repair of bone defects through synergistic osteogenesis promotion and osteoclastic inhibition. We believe that this hydrogel-based therapy strategy holds great promise in achieving simultaneous tumor inhibition and bone defect repair for postoperative osteosarcoma treatment.
研究领域:
肿瘤学
·
生物材料
·
药剂学
·
组织工程
✓ 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）