Advanced Healthcare Materials
·
2024
·
IF 10
Yinghua Gao,Zhuoying Wang,Xinmeng Jin,Xiaoli Wang,Yining Tao,Shandeng Huang,Yun Wang,Yingqi Hua,Xuran Guo,Jing Xu,Zhengdong Cai
Osteosarcoma (OS) is a “cold” tumor enriched in noninflammatory M2 phenotype tumor-associated macrophages (TAMs), which limits the efficacy of immunotherapy. The acidic tumor microenvironment (TME), generated by factors such as excess hydrogen (H + ) ions and high lactate levels, activates immunosuppressive cells, further promoting a suppressive tumor immune microenvironment (TIME). Therefore, a multitarget synergistic combination strategy that neutralizes the acidic TME and reprograms TAMs can be beneficial for OS therapy. Here, a calcium carbonate (CaCO 3 )/polydopamine (PDA)-based nanosystem (A-NPs@(SHK+Ce6)) is developed. CaCO 3 nanoparticles are used to neutralize H + ions and alleviate the suppressive TIME, and the loaded SHK not only synergizes with photodynamic therapy (PDT) but also inhibits lactate production, further reversing the acidic TME and repolarizing TAMs to consequently lead to enhanced PDT-induced tumor suppression and comprehensive beneficial effects on antitumor immune responses. Importantly, A-NPs@(SHK+Ce6), in combination with programmed cell death protein 1 (PD-1) checkpoint blockade, shows a remarkable ability to eliminate distant tumors and promote long-term immune memory function to protect against rechallenged tumors. This work presents a novel multiple-component combination strategy that coregulates the acidic TME and TAM polarization to reprogram the TIME.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Xu Yan,Qi Jingqi,Sun Wei,Zhong Wu,Wu Hongwei
Zoledronic acid (ZOL) has been approved as the only bisphosphonate for the prevention and treatment of metastatic bone diseases with acceptable safety and tolerability. However, systemic or direct injection of ZOL often causes severe side effects, which limits its clinical application. Here, an innovative nano-drug delivery system, ZOL-loaded hyaluronic acid/polyethylene glycol/nano-hydroxyapatite nanoparticles (HA-PEG-nHA-ZOL NPs), has been found to effectively inhibit the proliferation of three types of human osteosarcoma cell lines (143b, HOS, and MG63) at 1–10 μmol/L, while with low cell cytotoxicity on normal cells. The NPs significantly enhanced the apoptosis-related protein expression and tumor cell apoptosis rate. The NPs could also inhibit the proliferation of osteosarcoma cells by blocking the S phase of the cell cycle. In the orthotopic osteosarcoma nude mice model, local injection of the HA-PEG-nHA-ZOL NPs stimulated tumor necrosis, apoptosis, and granulocyte infiltration in the blood vessels. Altogether, the ZOL nano-delivery system possesses great potential for local treatment to prevent local tumor recurrence and can be applied in clinical osteosarcoma therapy.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物医学工程
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Xinglong Wang,Gongke Li,Ke Li,Yu Shi,Wenzheng Lin,Chun Pan,Dandan Li,Hao Chen,Jianwei Du,Huihui Wang
Targeted delivery of antitumor drugs has been recognized as a promising therapeutic modality to improve treatment efficacy, reduce the toxic side effects and inhibit tumor recurrence. In this study, based on the high biocompatibility, large specific surface area, and easy surface modification of small-sized hollow mesoporous silica nanoparticles β-cyclodextrin (β-CD)-benzimidazole (BM) supramolecular nanovalve, together with bone-targeted alendronate sodium (ALN) were constructed on the surface of small-sized HMSNs. The drug loading capacity and efficiency of apatinib (Apa) in HMSNs/BM-Apa-CD-PEG-ALN (HACA) were 65% and 25%, respectively. More importantly, HACA nanoparticles can release the antitumor drug Apa efficiently compared with non-targeted HMSNs nanoparticles in the acidic microenvironment of the tumor. In vitro studies showed that HACA nanoparticles exhibited the most potent cytotoxicity in osteosarcoma cells (143B cells) and significantly reduced cell proliferation, migration and invasion. Therefore, the drug-efficient release of antitumor effect of HACA nanoparticles is a promising way to treat osteosarcoma.
研究领域:
药理学
·
纳米技术
·
肿瘤学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hongzi Wu,Bowen Li,Jichun Shao,Qingquan Kong
The clinical use of chemotherapy for refractory osteosarcoma (OS) is limited due to its multiorgan toxicity. To overcome this challenge, new dosage forms and combination treatments, such as phototherapy, are being explored to improve targeted delivery and cytocompatibility of chemotherapeutic agents. In addition, inducing ferroptosis in iron-rich tumors could be a promising strategy to enhance OS therapy. In this study, a novel formulation was developed using natural biological H-ferritin (HFn) encapsulating the photosensitizer IR-780 and the chemotherapy drug gemcitabine (Gem) for OS-specific targeted therapy (HFn@Gem/IR-780 NPs). HFn@Gem/IR-780 NPs were designed to specifically bind and internalize into OS cells by interacting with transferrin receptor 1 (TfR1) which is overexpressed on the surface of OS cell membranes. The Gem and IR-780 were then released responsively under mildly acidic conditions in tumors. HFn@Gem/IR-780 NPs achieved cascaded antitumor therapeutic efficacy through the combination of chemotherapy and phototherapy under near-infrared irradiation in vitro and in vivo . Importantly, HFn@Gem/IR-780 NPs demonstrated excellent safety profile with significantly decreased drug exposure to normal organs, indicating its potential for reducing systemic toxicity. Thus, utilizing HFn as a vehicle to encapsulate highly effective antitumor drugs provides a promising approach for the treatment of OS metastasis and relapse.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Wang Mei-Ling,Cai Xu,Lv Feng,Li Jun,Chen Xue-Yu,Wang Meng-Yuan,Gu Ya-Chao,Tao Han-Lin,Liu Gang,Liu Xi-Qiu
Osteosarcoma (OS) research is constrained by a scarcity of clinical samples and traditional models that inadequately replicate the natural micro/nano-structure of bone. The role of these topological features in sustaining cellular function and influencing drug response remains insufficiently understood in OS. To address these challenges, a composite alginate-hydroxyapatite (AlgHA) cryogel was developed by incorporating bone-derived hydroxyapatite into an alginate-based cryogel matrix, which simultaneously enhanced mechanical stability and replicated the nano-topography of native bone extracellular matrix (ECM). The AlgHA-based OS model accurately reproduced key physiological characteristics, including cell proliferation, migration, and ECM protein remodeling. Notably, the model exhibited constitutive activation of multiple signaling pathways, such as PI3K-Akt, MAPK, and calcium signaling, which may be associated with malignant phenotypes. A comparative analysis of transcriptomic profiles and drug responses between 2D cultures and the AlgHA model has identified key pathways implicated in drug resistance, such as drug metabolism-cytochrome P450 and ATP-binding cassette transporters. Additionally, potential targets including receptor tyrosine kinases and PIK3CA, which are frequently overlooked in 2D cultures, were identified. These findings underscore the utility of the micro/nano-topological AlgHA cryogel as a physiologically relevant model for OS, facilitating mechanistic studies, therapeutic target identification, and drug sensitivity prediction. And this model presents a promising platform for advancing OS treatment strategies. Graphical
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 5.4
Jinku Guo,Yingfeng Cao,Kaipen Jin,Bing Liu,Wei Wang,Chen Chen,Jun Xie,Ankai Xu
BackgroundCyclovirobuxine D (CVB-D), an alkaloid from Buxus microphylla, exhibits anticancer effects in various tumors, but its role in osteosarcoma remains unexplored. This study investigates its efficacy and mechanism in osteosarcoma.MethodsWe screened a drug library and evaluated CVB-D’s effects on osteosarcoma cell lines using CCK-8 and colony formation assays. Saos2 and K7M2 cells were selected for further analysis. Flow cytometry assessed apoptosis and cell cycle. RNA-seq identified downstream pathways, including NF-kappaB, and stemness markers (CD24, ALDH1A1). Stemness was examined via serum-free suspension culture, and NF-kappaB pathway activator Diprovocim was used in rescue experiments. A xenograft mouse model validated the findings.ResultsCVB-D suppressed proliferation, stemness, and induced apoptosis in osteosarcoma. These effects may be partially mediated through the p-NF-kappaB2/NF-kappaB2 axis and were reversible upon NF-kappaB pathway activation.ConclusionCVB-D inhibits osteosarcoma possibly via the non-canonical NF-kappaB pathway, suggesting a potential therapeutic strategy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2026
·
IF 5.8
Liu Kai,Shen Hongliang,Li Jietao,Feng Yu,Zhou Chang,Jiang Anlong
Osteosarcoma remains a highly aggressive primary bone
malignancy,
and its clinical treatment is frequently limited by chemoresistance,
systemic toxicity, and insufficient tumor-specific drug accumulation.
To address these challenges, we developed an OS-7.9 aptamer-functionalized
ZIF-8 nanoscale platform for the targeted codelivery of sorafenib
(SFN) and GPX4 siRNA, designated O-SR-ZIF-8, with the intended application
of ferroptosis-based osteosarcoma therapy. The resulting nanoparticles
exhibited a uniform nanoscale size distribution, favorable colloidal
stability, high payload-loading capacity, and pH-responsive release
behavior. The ZIF-8 nanostructure remained relatively stable under
physiological conditions but promoted accelerated release of SFN and
GPX4 siRNA in acidic tumor-mimicking microenvironments, supporting
its suitability for tumor-localized delivery. Compared with nontargeted
formulations, O-SR-ZIF-8 markedly enhanced cellular internalization
in MG-63 osteosarcoma cells, inhibited cell proliferation, promoted
cell death, increased intracellular oxidative stress, and suppressed
migration and invasion. In a murine osteosarcoma xenograft model,
systemic administration of O-SR-ZIF-8 significantly restrained tumor
growth through GPX4 silencing and modulation of ferroptosis-related
signaling. Moreover, the nanoscale formulation exhibited favorable
biocompatibility, as evidenced by negligible hemolytic activity and
no obvious histopathological injury in major organs. Together, these
findings indicate that O-SR-ZIF-8 is an aptamer-guided nanoscale therapeutic
platform with potential in the treatment of osteosarcoma through targeted
delivery of sorafenib and GPX4 siRNA to silence genes and increase
oxidative stress associated with ferroptosis.
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR AND CELLULAR PROBES
·
2025
·
IF 3
Xin Song,Sihao Chen,Junning Cheng,Haiyu Li,Ruixin Wu,Min Yan,Min Wang,Jie Li,Aishun Jin,Wang Wang
Purpose Osteosarcoma (OS) exhibits limited immune cell infiltration that directly contributes to poor prognosis. This study sought to screen and identify pivotal biomarkers of OS immune infiltration and early diagnosis of OS. Methods The immune cell infiltration profiles with transcriptome sequencing data from 88 OS samples were explored with CIBERSORT algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network analyses were applied to identify hub genes, with the expressions confirmed by dual immunofluorescence in 50 OS samples. The new biomarker gene HTRA1 were examined by immunohistochemistry and validated by the Immune score and immune gene expression profile analyses. The impact of HTRA1 on OS prognosis was verified by Least absolute shrinkage and selection operator (LASSO) regression analysis. The biological effect of HTRA1 was characterized in MG63 cells. Result CD8 + T cells, activated memory CD4 + T cells and plasma cells were positively correlated with the prognosis of OS. Hub genes CCL5 , CXCL9 , CXCL13 , and HTRA1 , exhibited positive correlation with the infiltration of both CD8 + T cells and CD4 + T cells. HTRA1 expression was reduced in osteosarcoma tissues, which was positively correlated with immune scores and the expressions of immune-related genes. High levels of HTRA1 were associated with favorable OS prognosis, and could negatively impacted MG63 malignant characteristics. Conclusion CCL5 , CXCL9 , CXCL13, and HTRA1 were OS hub genes positively correlate with CD8 + T cell and CD4 + T cell infiltrations. HTRA1 can serve as an underlying biomarker for the prognosis and immunotherapy of OS.
研究领域:
肿瘤学
·
免疫学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Shanyi Lin,Hao Liu,Letian Lv,Guanyu Jin,Xinyu Xiang,Bingzheng Yu,Yuanzhen Su,Shucheng Zhang,Zijuan Wang,Zhaofan Yang,Luyao Wang,Linlin Liu,Shixian Lv,Wei Guo,Yu Guo
Sonodynamic therapy (SDT) is an emerging modality for cancer treatment that induces immunogenic cell death (ICD) through reactive oxygen species (ROS) generation, thereby triggering potent antitumor immunity. However, the hypoxic and glutathione (GSH)-rich tumor microenvironment restricts ROS production, while dense extracellular matrix (ECM) formed by cancer-associated fibroblasts (CAFs) further impedes immune cell infiltration. Here, we developed a hydrogel-based localized delivery platform co-encapsulating the nano-sonosensitizer PCN-224@MnO 2 @HA (PMH), and SIS3, a SMAD3 inhibitor. Upon hydrogel-mediated local administration, MnO 2 catalyzes O 2 generation from endogenous hydrogen peroxide while depleting intracellular GSH, thereby amplifying ROS production during SDT. Concurrently, SIS3 reprograms CAFs by blocking TGF-β/SMAD3 signaling, reducing collagen deposition and promoting immune cell infiltration. In an osteosarcoma mouse model, the combination of PMH-mediated SDT with SIS3-induced CAF reprogramming reduced collagen deposition by approximately 50 % and triggered robust antitumor immune responses, which collectively contributed to a 76 % inhibition of tumor growth. Collectively, this study demonstrates a novel CAF-targeted SDT strategy integrating ECM remodeling, ROS enhancement, and localized delivery, offering a promising therapeutic paradigm for solid tumor treatment.
研究领域:
肿瘤学
·
生物材料
·
免疫治疗
·
分子肿瘤学
·
转化医学
·
药剂学
·
肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Jianxin Hao,Xiaopeng Yu,Kai Tang,Xueru Ma,Hongxu Lu,Chengtie Wu
Recent advances in bone tissue engineering have shown promise for bone repair post osteosarcoma excision. However, conflicting research on mesenchymal stem cells (MSCs) has raised concerns about their potential to either promote or inhibit tumor cell proliferation. It is necessary to thoroughly understand the interactions between MSCs and tumor cells. Most previous studies only focused on the interactions between cells within the tumor tissues. It has been challenging to develop an in vitro model of osteosarcoma excision sites replicating the complexity of the bone microenvironment and cell distribution. In this work, we designed and fabricated modular bioceramic scaffolds to assemble into a co-culture model. Because of the bone-like composition and mechanical property, tricalcium phosphate bioceramic could mimic the bone microenvironment and recapitulate the cell-extracellular matrix interaction. Moreover, the properties for easy assembly enabled the modular units to mimic the spatial distribution of cells in the osteosarcoma excision site. Under this co-culture model, MSCs showed a noticeable tumor-stimulating effect with a potential risk of tumor recurrence. In addition, tumor cells also could inhibit the osteogenic ability of MSCs. To undermine the stimulating effects of MSCs on tumor cells, we present the methods of pre-differentiated MSCs, which had lower expression of IL-8 and higher expression of osteogenic proteins. Both in vitro and in vivo studies confirm that pre-differentiated MSCs could maintain high osteogenic capacity without promoting tumor growth, offering a promising approach for MSCs’ application in bone regeneration. Overall, 3D modular scaffolds provide a valuable tool for constructing hard tissue in vitro models. Statement of significance Bone tissue engineering using mesenchymal stem cells (MSCs) and biomaterials has shown promise for bone repair post osteosarcoma excision. However, conflicting researches on MSCs have raised concerns about their potential to either promote or inhibit tumor cell proliferation. It remains challenges to develop in vitro models to investigate cell interactions, especially of osteosarcoma with high hardness and special composition of bone tissue. In this work, modular bioceramic scaffolds were fabricated and assembled to co-culture models. The interactions between MSCs and MG-63 were manifested as tumor-stimulating and osteogenesis-inhibiting, which means potential risk of tumor recurrence. To undermine the stimulating effect, pre-differentiation method was proposed to maintain high osteogenic capacity without tumor-stimulating, offering a promising approach for MSCs’ application in bone regeneration.
研究领域:
组织工程
·
癌症生物学
·
干细胞研究
·
生物材料科学
✓ 已验证
DOI
PubMed
高影响因子
Biomedical Engineering-Biomedizinische Technik
·
2019
·Vol. 65
·期 2
·229-236
·
IF 1.007
Weifan Xu,Yi Lou,WangShenjie Chen,Yifan Kang
Effective cancer therapy usually requires the assistance of well-designed drug carriers. In order to increase the drug accumulation to tumor tissue as well as to reduce the side effects of drug carriers, the hybrid drug delivery system (DDS) was developed by integrating folic acid (FA) and a metal-organic framework (MOF). The anticancer drug doxorubicin (DOX) was preloaded into the MOF nanoparticles during the synthesis process of the MOF nanoparticles. After surface modification with FA, the resulting FA/MOF/DOX nanoparticles were capable of serving as a biocompatible osteosarcoma targeting a DDS to enhance the chemotherapy of osteosarcoma. The dynamic light scattering method revealed that the obtained FA/MOF/DOX nanoparticles were particles with a size around 100 nm. Moreover, FA/MOF/DOX nanoparticles could enhance the delivery efficacy of DOX into MG63 (human osteosarcoma) cells as compared to FA free nanoparticles (MOF/DOX), in which a folate receptor (FR) might be involved. It was worth mentioning that in vitro [methylthio tetrazole (MTT) study in the MG63 cells] and in vivo (anticancer study in the MG63 xenograft model) assays both revealed that FA/MOF/DOX nanoparticles possessed stronger anticancer capability than free DOX or MOF/DOX nanoparticles.
研究领域:
肿瘤学
·
药剂学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Bijiang Geng,Hua Qin,Wenwen Shen,Ping Li,Fuling Fang,Xiaokai Li,Dengyu Pan,Longxiang Shen
Osteosarcoma as an aggressive malignant neoplasm is commonly treated by surgical resection, chemotherapy, and radiotherapy, but surgery induces bone defects and chemo/radiotherapy causes severe systemic toxicity. We have designed a novel low-toxic bifunctional 0D/2D heterojunction (HJ) that can be used to generate effective photothermal effects in the second NIR window (NIR-II, 1000–1350 nm) for simultaneous osteosarcoma treatment and bone regeneration. To construct this 0D/2D nanostructure, biocompatible, positively charged NIR-II-responsive carbon dots (CDs) were synthesized by an ultrafast microwave-assisted hydrothermal method, followed by electrostatically driven assembly on both sides of negatively charged WS 2 nanosheets. We found that the HJs exhibited enhanced NIR-II absorption and photothermal conversion efficiency. Due to the deep-tissue penetration ability of 1064 nm laser, complete osteosarcoma ablation was realized at a low power density even when being covered by a 10-mm-thick additional tissue. Furthermore, osteogenic differentiation was remarkably enhanced by mild photothermal effects of CD/WS 2 HJs, which significantly up-regulated bone-related gene expressions, particularly, heat shock protein expression. Designed CD/WS 2 HJs can be used in osteosarcoma treatment and bone-tissue engineering.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
组织工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）