JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-15
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IF 10.2
Luo Tingting,Jiang Mingyang,Cheng Ziqiang,Lin Yuntao,Chen Yuling,Zhang Zhenyu,Zhou Jian,Zhou Wenhua,Yu Xue-Feng,Li Shuchun,Geng Shengyong,Yang Hongyu
As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS 3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.
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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ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Yunlong Ma,Lan Jiang,Jie Hu,Enjun Zhu,Nan Zhang
Osteosarcoma is a devastating malignant neoplasm that seriously threatens human health. After an osteosarcoma resection, the simultaneous treatment of tumor recurrence, postoperative infection, and large bone loss remains a formidable challenge clinically. Herein, a versatile multiscale therapeutic platform (Fs-BP-DOX@PDA) is engineered based on NiTi alloys with versatile properties for near-infrared (NIR)-mediated osteosarcoma synergistic photothermo-chemotherapy, bone regeneration, and bacterial elimination. First, an intriguing method for fabricating groovelike micro-nanostructures (Fs-NiTi) through femtosecond laser direct writing to enhance osseointegration with strong contact guidance is proposed. Then, black phosphorus (BP) nanosheets as gratifying photothermal conversion agents, osteogenetic agents, and a drug delivery platform are decorated on Fs-NiTi to construct multiscale hierarchical structures (Fs-BP). Finally, the polydopamine (PDA) modification is utilized to enhance the photothermal performance, biocompatibility, and chemical stability of doxorubicin (DOX)-loaded Fs-BP and endow NIR/pH-dual-responsive DOX release properties. Fs-BP-DOX@PDA effectively induces tumor cell (Saos-2 and MDA-MB-231) death in vitro, completely eradicates osteosarcoma in mice, and observably promotes bone-regeneration bioactivity. Furthermore, it possesses prominent antibacterial efficiencies toward Staphylococcus aureus (99.2%) and Pseudomonas aeruginosa (99.6%). Overall, this work presents a smart comprehensive fabrication methodology to construct a versatile multiscale therapeutic platform for multimodal osteosarcoma treatment and biomedical tissue engineering.
研究领域:
生物医学工程
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癌症治疗
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组织工程
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材料科学
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纳米技术
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PubMed
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2023
·
IF 6.2
Chenxiao Zhen,Jindou Li,Junyu Liu,Yi Lyu,Li Xie,Huanhuan Lv
Phenethyl isothiocyanate (PEITC), a kind of isothiocyanate available in cruciferous vegetables, exhibits inhibitory effects on cancers. PEITC has been extensively recorded for its effect on regulation of redox status in cancer cells. Our previous studies revealed that PEITC induced ROS-dependent cell death in osteosarcoma. Mitochondria are the main sites for ROS generation and play significant role in deciding cell fate. To dissect the mechanism of PEITC's action on osteosarcoma cells, we detected the changes on mitochondrial network, function and metabolism in K7M2 and 143B cells. Here, PEITC induced cytosolic, lipid and mitochondrial ROS production in osteosarcoma cells. It changed mitochondrial morphology from elongated to punctate network and decreased mitochondrial mass. Meantime, PEITC increased mitochondrial transmembrane potential in short time, decreased it with time prolonged, and later collapsed it in K7M2 cells, and reduced it in 143B cells. PEITC inhibited proliferation potential of osteosarcoma cells with damage on mitochondrial respiratory chain complexes. Further, PEITC-treated osteosarcoma cells experienced a sudden increase in ATP level, and later its content was decreased. Moreover, PEITC downregulated the expressions of mitochondrial respiratory chain complexes including COX IV, UQCR, SDHA and NDUFA9 in 143B cells and COX IV in K7M2 cells. At last, by using ρ 0 cells derived from K7M2 and 143B cells, we found that osteosarcoma cells that depleted mtDNA were less sensitive to PEITC-induced changes on cellular morphology, cytoskeleton filament, mitochondrial transmembrane potential and ROS generation. In conclusion, our study demonstrated that mitochondria may play important role in PEITC-induced oxidative cell death in osteosarcoma cells.
研究领域:
肿瘤学
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细胞生物学
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医学
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DOI
PubMed
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2026
·
IF 5.4
Li Wang,Jiaqi Chen,Simin Gou,Yuting Long,Dandan Yang,Jifang Zhou,Yaxin Zheng,Wan Yan,Xuzhi Hu
Postoperative tumor recurrence and chemoresistance in osteosarcoma treatment highlight the urgent need to develop localized implants, particularly large-scale scaffolds capable of selectively eliminating residual tumor cells, minimizing significant trauma during implantation. In this study, a drug-loaded intelligent scaffold system was designed for minimally invasive surgical implantation, enabling localized sustained release of the anticancer drug paclitaxel (PTX). This material system was fabricated into a three-dimensional porous scaffold via in situ polymerization combined with gas foaming technology. Citrate-functionalized amorphous calcium phosphate (CACP) was incorporated into the polyurethane (PU) scaffold, serving as an antibacterial agent while enhancing osteogenic expression. Following surface modification with polydopamine (PDA), PTX-Lips were covalently immobilized onto the modified scaffold surface. The resulting scaffold exhibited an extracellular matrix-mimicking highly porous structure, provided good mechanical support, and demonstrated excellent shape memory properties at 37°C. Comprehensive in vitro and in vivo studies confirmed that the drug-loaded scaffold exhibited three key functionalities: sustained drug release kinetics; significant tumor cell inhibitory efficacy; and biocompatibility supporting normal cell adhesion. Crucially, animal models unequivocally demonstrated its effectiveness in preventing postoperative local tumor recurrence and suppressing distant metastasis. This scaffold provided an efficient synergistic strategy for postoperative osteosarcoma treatment by integrating localized chemotherapy with tissue regeneration support.
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International Journal of Nanomedicine
·
2023
·
IF 8
Hongxiang Wei,Jinyuan Chen,Shenglin Wang,Feihuan Fu,Xia Zhu,Chaoyang Wu,Zhoujie Liu,Guangxian Zhong,Jianhua Lin
Purpose The primary goal of the present study was to develop the nano-drug consisting of doxorubicin and exosome derived from mesenchymal stem cells, and to explore its effect on osteosarcoma in vitro.Methods The exosomes were isolated from bone marrow MSCs (BM-MSCs) by an Exosome Isolation Kit. The exosome-loaded doxorubicin (Exo-Dox) was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) were used to characterize of the exosome and Exo-Dox. The cytotoxicity of Exo-Dox was determined by CCK-8 assay. Further, the cellular uptake of different drugs was analyzed using inverted fluorescence microscope and flow cytometry.Results The typical exosome structures can be observed by TEM. After loading with doxorubicin, its size is larger than free exosome. Compared with the free Dox, the prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line.Conclusion The prepared Exo-Dox could be used as an excellent chemotherapeutic drug for treatment of osteosarcoma in vitro. Considering the tumor-homing feature of BM-MSCs, the Exo-Dox may be a good candidate for targeted osteosarcoma treatment in future study.
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JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-13
·
IF 9.429
Wang Yongtao,Wang Nana,Yang Yingjun,Chen Yazhou,Zhang Zhengguo
Gene transfection was supposed to be the most promising technology to overcome the vast majority of diseases and it has been popularly reported in clinical applications of gene therapy. In spite of the rapid development of novel transfection materials and methods, the influence of morphology-dependent nanomechanics of malignant osteosarcoma on gene transfection is still unsettled. In this study, cell spreading and adhesion area was adjusted by the prepared micropatterns to regulate focal adhesion (FA) formation and cytoskeletal organization in osteosarcoma cells. The micropattern-dependent FA and cytoskeleton could induce different cellular nanomechanics to affect cell functions. Our results indicated that transfection efficiency was improved with enlarging FA area and cell nanomechanics in micropatterned osteosarcoma. The difference of gene transfection in micropatterned cells was vigorously supported by cellular internalization capacity, Ki67 proliferation ability and YAP mechanotranduction through the regulation of focal adhesion and cytoskeletal mechanics. This study is an attempt to disclose the relationship of cell nanomechanics and gene transfection for efficient gene delivery and develop multifunctional nanomedicine biomaterials for accurate gene therapy in osteosarcoma cells.
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PubMed
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PeerJ
·
2021
·
IF 2.984
Yufan Zhu,Zhiqiang Yang,Yuanlong Xie,Min Yang,Yufeng Zhang,Zhouming Deng,Lin Cai
Objective This study aims to explore the effect of daidzein, which is a natural isoflavone compound mainly extracted from soybeans, on osteosarcoma and the potential molecular mechanism. Material and Methods 143B and U2OS osteosarcoma cells were treated with gradient concentrations of daidzein, and MTT assay was used to determine the cell proliferation capacity and IC 50 . Hoechst 33342 staining and Annexin V-FITC/PI detection were used to determine apoptosis. Cell cycle was analyzed by flow cytometry, and migration ability were detected by transwell assays and scratch wound assay. An osteosarcoma xenograft mice model was applied to investigate the effect of daidzein on osteosarcoma in vivo . Systematic pharmacology and molecular modeling analysis were applied to predict the target of daidzein to osteosarcoma, and the target Src was verified by western blotting. We also observed the effect of daidzein on cell proliferation and apoptosis of Src-overexpressing osteosarcoma cells. Results In vitro , daidzein significantly inhibited 143B and U2OS osteosarcoma cell proliferation and migration, and induced cell cycle arrest. In vivo , daidzein exerts antitumor effects in osteosarcoma xenograft mice. After systematic screening and analysis, Src-MAPK signaling pathway was predicted as the highest-ranked pathway. Western blot demonstrated that daidzein inhibited phosphorylation of the Src-ERK pathway in osteosarcoma cells. Also, overexpression of Src could partially reverse the inhibitory effects of daidzein on osteosarcoma cell proliferation. Conclusion Daidzein exerts an antitumor effect on osteosarcoma, and the mechanism may be through the Src-ERK pathway.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2020
·
IF 5.162
Hao Wu,Yuan Luo,Dongmei Xu,Xue Ke,Tianyuan Ci
The standard-of-care chemotherapy is important in the treatment of osteosarcoma and bone metastastic tumors. However, the efficacy is limited by the specific physiological environment of the bone. Thus, developing an efficient antitumor and anti-metastasis chemotherapeutic formulation is desired for treatment of bone tumors. Herein, we utilized the alendronate (ALN) and low molecular weight heparin (LMWH) modified liposomes to deliver the antitumor drug doxorubicin (DOX), where traditionally-believed non-active drug carrier, targeting moiety could also exhibit biological functions and realize anti-tumor and anti-metastasis efficiency synergistically with the antitumor drug. Specifically, ALN could serve as the bone targeting moiety and the therapeutic agents of anti-osteoporosis. LMWH could enhance the blood circulation time of liposomes and exhibit anti-metastasis efficiency. Besides characterization of typical physiochemical properties of the delivery system, both the orthotopic osteosarcoma model and bone metastasis cancer model were adopted to evaluate the in vivo efficacy. The results proved this system could remarkably suppress tumor growth and inhibit tumor metastasis.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2022
·Vol. 45
·期 12
·1733-1742
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IF 2.264
Yongbin Jing,Mingkun Jia,Jinpeng Zhuang,Dong Han,Changlong Zhou,Jinglong Yan
Osteosarcoma (OS) is the most common primary malignant bone tumor and is mainly diagnosed in children. Toll-like receptor 9 (TLR9) is expressed in various tumor cells and was correlated with cancer progression. However, the underlying mechanism of TLR9 on the OS progression remains unclear. Our previous study demonstrated that the expression of TLR9 was positively correlated with the development stage of OS. Herein, we further evaluated the actual roles and the molecular mechanism of TLR9 on regulating OS cell proliferation and metastasis. Our data showed that TLR9 was upregulated in OS cells compared to normal osteoblastic cells, and knockdown of TLR9 inhibited OS cell proliferation and induced cell cycle arrest by the decreased expression of cyclin D1, CDK2, and p-Rb, while TLR9 overexpression exerted the inverse effects. Furthermore, TLR9 overexpression could enhance the migration and invasion activities of the OS cells by the upregulation of matrix metalloproteinases 2 (MMP2) and MMP9, and the opposite result was observed in TLR9-silenced cells. Moreover, the nuclear factor kappa B (NF-κB) signaling pathway was activated by TLR9, and TLR9-induced malignant phenotype of OS cells was abrogated by the NF-κB antagonist BAY11-7082. Our study indicated that TLR9 might play a critical role in facilitating OS progression by activating the NF-κB signaling pathway, which may provide a valuable therapeutic target for OS.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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癌症研究
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DOI
PubMed
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ACS Omega
·
2026
·
IF 5.2
Zhiyu Chen,Junhong Chen,Shuang Liu,Xu Zhou,Yichuan Zhang,Yunsheng Jiang,Xiao Liu,Yuan Zhang,Xiangling Pu,Hui Zhang
Osteosarcoma is the most prevalent primary bone cancer affecting children and adolescents, characterized by its high invasiveness and the challenges in treatment posed by multidrug resistance. Cancer stem cells significantly contribute to poor clinical outcomes; however, current targeted therapies remain limited in their effectiveness. In this study, we developed a novel dual-responsive nanomedicine designed to target the microenvironment of osteosarcoma cancer stem cells (OCSCs) and osteosarcoma itself, which selectively releases all-trans retinoic acid and paclitaxel, termed mPCDAP. Our findings indicate that mPCDAP rapidly releases all-trans retinoic acid to suppress stemness under conditions of elevated glutathione, subsequently increasing intracellular reactive oxygen species levels in tumor cells. This mechanism further facilitates the release of paclitaxel under conditions of highly reactive oxygen species, thereby inducing apoptosis in osteosarcoma cells. Additionally, mPCDAP was effectively internalized by both osteosarcoma cells and OCSCs, with in vitro and in vivo results demonstrating significant synergistic antitumor effects, promoting apoptosis and markedly reducing tumor stemness. This study presents a novel approach and promising prospects for targeted therapy of osteosarcoma and OCSCs.
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Journal of Magnesium and Alloys
·
2026
·
IF 13.8
Dong Li,Tong Zhang,Shaosheng Jia,Jianan Yu,Rongbang Sun,Bin Yin,Liguo Wang,Lingchuang Bai,Lan Chen,Shaokang Guan
Osteosarcoma (OS) poses a severe threat to human health, and the standard clinical treatment involves prosthetic replacement after surgical removal combined with radiotherapy and chemotherapy. However, the recurrence of residual tumors and extensive bone defects leads to a poor prognosis for patients. Zoledronic acid (ZA) is clinically used for tumor treatment and osteoclast inhibition. Nevertheless, intravenous infusion of ZA has poor targeting and significant toxicity to normal tissues. Biodegradable Mg alloys have excellent mechanical and biological compatibility, making them ideal for orthopedic implants. However, their application is limited due to poor corrosion resistance. This work applied a multi-composite layered double hydroxide (LDH)-ZA/PDA coating to the surface of ZE21C alloy. The composite coating adsorbed ZA in weakly alkaline or neutral conditions and released ZA under near-infrared (NIR) irradiation in the tumor microenvironment (TME). The stimuli-responsive release of ZA was confirmed to be related to the NIR-TME-triggered change in LDH interlayer spacing. In vitro and in vivo experiments showed that this multi-composite coating improved corrosion resistance, responded to TME and NIR stimuli to release ZA and reactive oxygen species, effectively targeting and killing tumor cells and osteoclasts through the AKT/GSK-3β signaling pathway. It also transformed OS from “cold tumors” into “hot tumors”, reactivated macrophage-mediated tumor immunity, and promoted osteogenesis. The chemo-thermal-therapeutic approach of the composite coating achieves a “three-birds-with-one-stone” effect. This study offers new insights into applying Mg alloys in prosthetic replacements after OS surgery.
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
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2026
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IF 4
Zhewen Deng,Mengyuan Zhang,Senqiang Zhu,Yunlong Zhang,Haitao Liao,Jiaqi Li,Peiyu Yan,Qi Zhang,Rui Liu,Bo Ma
Osteosarcoma (OS), a highly aggressive bone cancer with a dismal prognosis in the metastatic setting, urgently demands novel therapeutic modalities. While phototherapy offers a promising, minimally invasive strategy, its clinical efficacy is often hampered by the poor aqueous solubility of photosensitizers and the development of multidrug resistance. In response, we constructed the dual-modal nanoplatform BDP-NPs by leveraging a multifunctional F127/TPGS mixed micelle to encapsulate a cationic BODIPY photosensitizer, thereby creating a system engineered for enhanced tumor accumulation and to overcome multidrug resistance. Benefiting from their uniform size, colloidal stability, and hypoxia-responsive properties, the BDP-NPs demonstrate potent reactive oxygen species generation and high photothermal conversion efficiency under 525 nm laser irradiation. This dual-modal action induces severe mitochondrial dysfunction, thereby triggering apoptosis in both 3D tumor spheroids and tumor tissues. The synergistic phototherapy elicited profound mitochondrial-targeted cytotoxicity, inhibited clonogenic survival, and significantly suppressed tumor growth in human osteosarcoma models, all while maintaining a favorable biosafety profile. Mechanistic analyses revealed that this synergistic phototherapy plays a pivotal role in suppressing the YAP1/β-catenin axis, thereby reversing the epithelial-mesenchymal transition (EMT) program and consequently inhibiting OS cell proliferation, migration and invasion. This study not only establishes BDP-NPs as a potent and biocompatible nanotherapeutic for OS but also presents a groundbreaking phototherapeutic strategy to disrupt the YAP1/β-catenin axis-a key signaling network driving tumorigenesis and malignant progression. This approach provides a robust conceptual foundation for devising next-generation phototherapeutics that precisely target oncogenic signaling in aggressive cancers.
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