ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Ce Zhu,Miaomiao He,Dan Sun,Yong Huang,Leizhen Huang,Meixuan Du,Jingcheng Wang,Juehan Wang,Zhongyang Li,Bowen Hu,Yueming Song,Yubao Li,Ganjun Feng,Limin Liu,Li Zhang
In this work, we developed the first 3D-printed polyetheretherketone (PEEK)-based bone scaffold with multi-functions targeting challenging bone diseases such as osteosarcoma and osteomyelitis. A 3D-printed PEEK/graphene nanocomposite scaffold was deposited with a drug-laden (antibiotics and/or anti-cancer drugs) hydroxyapatite coating. The graphene nanosheets within the scaffold served as effective photothermal agents that endowed the scaffold with on-demand photothermal conversion function under near-infrared laser irradiation. The bioactive hydroxyapatite coating significantly boosted the stem cell proliferation in vitro and promoted new bone growth in vivo. The presence of antibiotics and anti-cancer drugs enabled eradication of drug-resistant bacteria and ablation of osteosarcoma cancer cells, the treatment efficacy of which can be further enhanced by on-demand laser-induced heating. The promising results demonstrate the strong potential of our multi-functional scaffold in applications such as bone defect repair and multimodal treatment of osteosarcoma and osteomyelitis.
研究领域:
生物医学工程
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材料科学
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骨科
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癌症研究
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感染性疾病
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DOI
PubMed
高影响因子
DRUG DELIVERY
·
2020
·
IF 4.902
Renna Qiu,Denghua Sun,Yuzhuo Bai,Jiannan Li,Lizhe Wang
Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence. Currently, surgery combined with chemotherapy is the main treatment for osteosarcoma. However, the long-term survival of patients with metastatic osteosarcoma is unsatisfactory. Therefore, new treatment methods to improve the prognosis of patients with osteosarcoma are required. The present study aimed to develop nanocarriers with both tumor targeting and reduction responsiveness abilities, and to improve the therapeutic effect and reduce toxicity by loading traditional small molecule antitumor drugs. The tumor targeting peptide-decorated, doxorubicin (DOX)-loaded mPEG-P(Phe-co-Cys) nanoparticles were developed successfully through the ring-opening polymerization of amino acids. The peptide VATANST (STP) can specifically bind with vimentin, which is highly expressed on the osteosarcoma cell surface, resulting in tumor targeting effects. The nanoparticle is core–shell structured to protect the loaded DOX during blood flow. The disulfide bonds within the nanoparticles are sensitive to the osteosarcoma microenvironment, which has high glutathione (GSH) levels. Under the enhanced permeability and retention and active tumor targeting effects, the STP-decorated DOX-loaded nanoparticles accumulated in tumor tissues. High GSH levels can rupture disulfide bonds, resulting in the controlled release of DOX, which will cause necrosis of tumor cells. The characteristics of the synthesized nanoparticles, DOX release profiles in vitro and in vivo, cytotoxicity analysis, animal study, and safety evaluation were performed. The nanoparticles could increase the tumor inhibition efficiency against osteosarcoma and reduce the side effects of DOX to major organs. The STP-decorated mPEG-P(Phe-co-Cys) nanoparticles might be a suitable drug delivery system for DOX to treat osteosarcoma.
研究领域:
药学
·
肿瘤学
·
生物材料学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yanhai Xi,Tingwang Jiang,Yinglan Yu,Jiangmin Yu,Mintao Xue,Ning Xu,Jiankun Wen,Weiheng Wang,Hailong He,Yan Shen,Daquan Chen,Xiaojian Ye,Thomas J Webster
Introduction Curcumin (CUR) is a general ingredient of traditional Chinese medicine, which has potential antitumor effects. However, its use clinically has been limited due to its low aqueous solubility and bioavailability. In order to improve the therapeutic effect of CUR on osteosarcoma (i.e., bone cancer), a multifunctional micelle was developed here by combining active bone accumulating ability with tumor CD44 targeting capacity.Methods The CUR loaded micelles were self-assembled by using alendronate-hyaluronic acid-octadecanoic acid (ALN-HA-C18) as an amphiphilic material. The obtained micelles were characterized for size and drug loading. In addition, the in vitro release behavior of CUR was investigated under PBS (pH 5.7) medium containing 1% Tween 80 at 37℃. Furthermore, an hydroxyapatite (the major inorganic component of bone) affinity experiment was studied. In vitro antitumor activity was evaluated. Finally, the anti-tumor efficiency was studied.Results The size and drug loading of the CUR loaded ALN-HA-C18 micelles were about 118 ± 3.6 nm and 6 ± 1.2%, respectively. CUR was released from the ALN-HA-C18 micelles in a sustained manner after 12 h. The hydroxyapatite affinity experiment indicated that CUR loaded ALN-HA-C18 micelles exhibited a high affinity to bone. CUR loaded ALN-HA-C18 micelles exhibited much higher cytotoxic activity against MG-63 cells compared to free CUR. Finally, CUR loaded ALN-HA-C18 micelles effectively delayed anti-tumor growth properties in osteosarcoma bearing mice as compared with free CUR.Conclusion The present study suggested that ALN-HA-C18 is a novel promising micelle for osteosarcoma targeting and delivery of the hydrophobic anticancer drug CUR.
研究领域:
药学
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生物医学工程
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2023
·
IF 0
Jiafei Gu,Xiaoling Liu,Ping Cui,Xiaosu Yi
For the treatment of tumor-related bone defects resulting from surgical resection, simultaneous eradication of residual tumor cells and repair of bone defects represent a challenge. To date, photothermal therapy based on photothermal materials is used to remove residual tumor cells under near infrared light. However, most of photothermal materials have no function for bone repair, and even if combined with bioactive materials to enhance osteogenesis, they still cause potential harm to the body due to inability to degrade or poor degradability. Herein, multifunctional bioactive glasses (PGFe5-1100, PGCu5-1100) based on phosphate glass doped with transition metal elements were prepared for photothermal ablation, bone regeneration, and controllable degradation. The glasses exhibited excellent photothermal effect, which was derived from the electron in-band transition after light absorption due to energy level splitting of doped transition metal element and the subsequent electron nonradiative relaxation. The photothermal performance can be controlled by laser power density, element doping content and glass melting temperature. Moreover, the hyperthermia induced by the glasses can effectively kill tumor cells in vitro. In addition, the glasses degraded over time, and the released P, Ca, Na, Fe could promote bone cell proliferation and osteogenic differentiation. Therefore, these results successfully demonstrated that transition metal element-doped phosphate glasses have multifunctional abilities of tumor elimination, bone regeneration, and spontaneous degradation simultaneously with better biosecurity and bioactivity, which is believed to pave the way for the design of novel biomaterials for osteosarcoma treatment.
研究领域:
生物材料
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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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生物医学工程
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产品关联
DOI
PubMed
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Ying Wang,Gareth R. Williams,Yilu Zheng,Honghua Guo,Shiyan Chen,Rong Ren,Tong Wang,Jindong Xia,Li-Min Zhu
One of the major challenges in effective cancer therapy arises because of the hypoxic microenvironment in the tumor. This compromises the efficacy of both chemo- and radiotherapy , and thus hinders patient outcomes. To solve this problem, we constructed polydopamine (PDA)-cloaked Fe-based metal organic frameworks (MOFs) loaded with d -arginine ( d -Arg), glucose oxidase (GOX), and the chemotherapeutic drug tirapazamine (TPZ). These offer simultaneous multifaceted therapy combining chemodynamic therapy (CDT)/radiotherapy (RT)/starvation therapy (ST)/gas therapy (GT) and chemotherapy. The particles further can act as contrast agents in magnetic resonance imaging. GOX catalyses the conversion of endogenous glucose and O 2 to hydrogen peroxide and gluconic acid , blocking the cells’ energy supply and providing ST. With the resultant acidification of the local environment, the breakdown of the MOF releases TPZ (for chemotherapy) and Fe 3+ , which reacts with H 2 O 2 to produce reactive oxygen species and thus stimulates the conversion of d -Arg to NO for GT and RT sensitization. The PDA coating not only seals the pores and chelates Fe 3+ to enhance the T 1 -weighted magnetic resonance imaging (MRI) properties, but also is used to graft folate bovine serum albumin (FA-BSA) and thereby target the tumor site. The combined administration of low doses of X-ray irradiation and nanoparticles reduces the side effects on healthy tissue and can prevent lung metastases in mice. This work highlights the synergistic treatment of osteosarcoma via ST/GT/CDT/RT/MRI/ chemotherapy using a PDA-cloaked MOF system.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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材料科学
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医学成像
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Tian-Tian Zhao,Tian-Jiao Zhou,Chen Zhang,Ying-Xuan Liu,Wen-Jia Wang,Chengjun Li,Lei Xing,Hu-Lin Jiang
Chemotherapy is the main treatment method for osteosarcoma in the clinic. However, drug resistance and its poor antimetastatic effects greatly limit its clinical application. In this work, dual-drug nanoparticles (NPs) containing albendazole (ABZ) and doxorubicin (DOX), named AD@PLGA–PEG NPs, were prepared to solve the problems of chemotherapeutic drug resistance and poor antimetastasis effects. Compared with free DOX, ABZ combined with DOX can increase intracellular reactive oxygen species (ROS) and induce more tumor cell apoptosis; therefore, AD@PLGA–PEG NPs produced more mitochondria-mediated oxidative stress and better apoptosis efficiency. Importantly, ABZ can also effectively inhibit the expression of hypoxia inducible factor-1α (HIF-1α) and then reduce the expression of its downstream vascular endothelial growth factor (VEGF); thus, the AD@PLGA–PEG NPs effectively inhibited tumor metastasis in vivo. Collectively, the dual-drug AD@PLGA–PEG NPs delivery system provided prominent antitumor and antimetastatic efficacy and might be a promising treatment for osteosarcoma.
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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癌症生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Jiangbo Nie,Yuhang Ling,Mingchao Jin,Zhuo Chen,Wei Liu,Weiyun Shen,Tianshun Fang,Jianyou Li,Ying He
Osteosarcoma (OS) is a highly fatal bone tumor characterized by high degree of malignancy and early lung metastasis. Traditional chemotherapy fails in improving the efficacy and survival rate of patients with OS. Butyrate (NaBu) has been reported as a new antitumor drug for inhibiting proliferation and inducing apoptosis in various cancer cells. However, the effect of NaBu on the ferroptosis of osteosarcoma is still unknown. This study aimed to investigate whether NaBu promotes erastin-induced ferroptosis in OS cells and to uncover the underlying mechanism. Here, we found that NaBu significantly enhanced erastin-induced ferroptosis in vitro . Compared with the group that erastin used alonely, pre-treating with NaBu exacerbated erastin-meditated GSH depletion, lipid peroxidation, and mitochondrial morphologic changes in OS cells. In a subcutaneous OS model, NaBu combined with erastin significantly reduced tumor growth and increased the levels of 4-HNE. Mechanistically, NaBu downregulated SLC7A11 transcription via regulating ATF3 expression. Overexpression of ATF3 facilitated erastin to induce ferroptosis, while ATF3 knockdown attenuated NaBu-induced ferroptosis sensitivity. In conclusion, our findings revealed a previously unidentified role of NaBu in erastin-induced ferroptosis by regulating SLC7A11, suggesting that NaBu may be a potential therapeutic agent for OS treatment.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2018
·Vol. 15
·期 4
·5250-5256
·
IF 1.664
Jun‑Ming Chen,Jue Zhang,Yong‑Mei Xia,Xiao‑Xia Wang,Jian Li
Steviol is the colonic metabolite of the natural sweetener steviol glycosides. It does not diffuse to the blood and the half maximal inhibitory concentration of steviol is longer compared with that of current chemotherapy agents, including 5‑fluorouracil and doxorubicin. The present study demonstrated that steviol inhibits the proliferation of the human osteosarcoma U2OS cell line in a dose‑ and time‑dependent manner, and that the inhibition rate is comparative with that of doxorubicin and 5‑fluorouracil. The mechanism of this anticancer activity is also investigated. The results indicated that steviol inhibits U2OS cells through inducing G1 phase cell cycle arrest, downregulating the ability of colony formation via a mitochondrial apoptotic pathway, which was indicated by an increase of the Bax/Bcl‑2 ratio and activation of cyclin‑dependent kinase inhibitor 1, tumor protein 53 and cyclin‑dependent kinase; whereas a Survivin and Caspase 3‑independent mechanism was involved. Considering that steviol appears minimally in the plasma during metabolism, and possesses a median lethal dose of 100-fold greater compared with that of 5‑fluorouracil, it may become a potential chemotherapy agent.
研究领域:
肿瘤学
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药理学
·
代谢
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DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 9
·3319-3333
·
IF 6.843
Mengyu Yao,Qingxia Zou,Wenwu Zou,Zhenze Xie,Zhihao Li,Xiujuan Zhao,Chang Du
The bifunctional tissue engineering scaffold with anti-tumor and bone repair properties is promising for the therapy of bone tumor where large bone defects often occur. In this study, hydroxyapatite (HA), poly(dopamine) (PDA), and carboxymethyl chitosan (CMCS) composite scaffolds were prepared by the 3D-printing technology. PDA significantly improved the rheological properties of the slurry for molding, mechanical properties, surface relative potential, and water absorption of composite scaffolds. The osteogenic properties of HA/PDA/CMCS composite scaffolds were evaluated by the cell experiment in vitro. The photothermal properties and anti-tumor effects of the scaffolds in vivo were assessed by the tumor model in nude mice. HA/PDA/CMCS composite scaffolds could promote more osteogenic differentiation of mouse bone marrow stromal cells (mBMSCs) than scaffolds without PDA in vitro and the effect was not hindered by the photothermal process. The PDA-modified composite scaffold had excellent photothermal properties. Cell experiments showed that scaffolds with PDA under irradiation could suppress the tumor effectively. In vivo anti-tumor effects in nude mice indicated that the HA/PDA/CMCS composite scaffold promoted cell apoptosis/necrosis by the direct photothermal effect. Vascular injury was developed subsequently, which lead to the suppression of tumor cell proliferation due to hypoxia-ischemia. HA/PDA/CMCS composite scaffolds with multiple effects have great potential application in bone tumor therapy.
研究领域:
生物医学工程
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材料科学
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组织工程
·
肿瘤学
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DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Xuelei Yin,Shuaishuai Feng,Yingying Chi,Jinhu Liu,Kaoxiang Sun,Chuanyou Guo,Zimei Wu
An estrogen (ES)-functionalized cationic liposomal system was developed and exploited for targeted delivery to osteosarcoma. Natural biocompatible chotooligosaccharides (COS, MW2-5 KDa) were covalently tethered to the liposomal surface through a disulfate bond (-SS-) to confer reduction-responsive COS detachment, whereas estrogen was grafted via polyethylene glycol (PEG 2 K) chain to achieve estrogen receptor-targeting. The liposomal carriers were prepared by the ethanol injection method and fluorescent anticancer drug doxorubicin (DOX) was loaded with ammonium sulfate gradient. The physicochemical properties, reduction-sensitivity, and the roles of estrogen on cellular uptake and tumor-targeting were studied. The Chol-SS-COS/ES/DOX liposomes were spherical with an average size about 110 nm, and high encapsulation efficiency. The liposomes were stable in physiological condition but rapidly release the payload in response to tumoral intracellular glutathione (20 mM). MTT cytotoxicity assay confirmed that Chol-SS-COS/ES/DOX liposomes exhibited higher cytotoxicity to MG63 osteosarcoma cells than to liver cells (LO2). Flow cytometry (FCM) and confocal laser scanning microscopy revealed that cellular uptake of Chol-SS-COS/ES/DOX liposomes by MG63, than the free DOX or Chol-SS-COS/DOX. Ex vivo fluorescence distribution study showed that the multifunctional liposomes selectively accumulated in the MG63 xenografts versus the organs. Chol-SS-COS/ES/DOX liposomes strongly inhibited the tumor growth and enhanced the animal survival rate. Overall, the COS grafted estrogen-functionalized cationic liposomes, fortified with glutathione-responsiveness, showed great potential for specific intracellular drug delivery to estrogen receptor-expressing tumors such as osteosarcoma.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药物递送系统
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DOI
PubMed
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 3.978
Xing Sun,Zhiyuan Meng,Qingwen Yu,Xinyu Wang,Zheng Zhao
After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. Combination therapy based on a nanoparticle-based drug delivery system shows great promise in osteosarcoma therapy. In this study, we designed a multifunctional chitosan (CS) nanoparticle , which combined photothermal therapy (PTT) with chemotherapy to synergistically enhance osteosarcoma therapy and bone repair . Curcumin (CM) loaded CS nanoparticles were prepared through ionotropic gelation method and were further functionalized with polydopamine (PDA) coating to form CS-CM-PDA nanoparticles (CCPNPs). The CCPNPs displayed pH- and near-infrared (NIR)- responsive CM release behavior. In vitro anti-cancer results indicated that CCPNPs possessed a long-term stable anti-cancer effect compared to pure CM. The presence of the NIR irradiation combined with CCPNPs resulted in a dramatic decrease in MG-63 osteosarcoma cell viability in 10 min compared with the pure CCPNPs at the concentration of 500 μg/mL. Meanwhile, in vitro study demonstrated that CCPNPs induced MG-63 cell apoptosis via downregulating the expression of Bcl-2 and upregulating the expression levels of Bax and Caspase-3. Besides, CCPNPs could positively induce the proliferation of MC3T3-E1 osteoblast cells in vitro . These results suggested that CCPNPs with bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration .
研究领域:
纳米技术
·
肿瘤学
·
生物医学工程
·
再生医学
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DOI
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Fei Jia,Yu Liu,Xinyu Dou,Chuanchao Du,Tianli Mao,Xiaoguang Liu
Osteosarcoma (OS) is the most common malignancy of bone. Liensinine exerts antitumor effects on cancers of the colon, breast, and gallbladder. However, its antitumor activity in OS remains unclear. This study is aimed at investigating the efficacy of liensinine against OS and the underlying mechanism of action. Cell proliferation, apoptosis, and cycle arrest in OS were detected using the Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays, respectively. The production of reactive oxygen species (ROS), glutathione (GSH) and glutathione disulfide (GSSG) concentrations, and mitochondrial membrane potential (MMP) of OS cells were measured by flow cytometry, colorimetry, and JC-1 staining. The expressions of factors related to apoptosis, cell cycle, and activation of the JAK2/STAT3 pathway were determined by Western blotting. To examine the potential role of ROS, an antioxidant (N-acetyl cysteine, NAC) was used in combination with liensinine. In vivo, we generated a xenograft mouse model to assess its antitumor efficacy. Tissue level expressions of factors related to apoptosis and activation of the JAK2/STAT3 pathway were assessed by immunohistochemistry or Western blotting. Liensinine inhibited the proliferation and induced G0/G1 phase arrest and apoptosis of OS cells in a dose-dependent manner. Additionally, liensinine promoted intracellular ROS production, enhanced the GSSG/GSH ratio, and induced MMP loss and ROS-mediated suppression of the JAK2/STAT3 pathway. NAC significantly attenuated the liensinine-induced antitumor activities and activated the JAK2/STAT3 pathway. In vivo, liensinine effectively inhibited the OS growth and promoted apoptosis; however, it had no negative effect on the internal organs. In conclusion, liensinine-induced ROS production could suppress the activation of the JAK2/STAT3 pathway and inhibit the OS growth both in vivo and in vitro. Our findings provided a new rationale for subsequent academic and clinical research on OS treatment.
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DOI
PubMed
高影响因子
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