Biomaterials Science
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2022
·Vol. 10
·期 7
·1831-1843
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IF 7.59
Ting Ge,Zhang Weiwei,Fei Ge,Longbao Zhu,Ping Song,Wanzheng Li,Lin Gui,Wan Dong,Yugui Tao,Kai Yang
Chemotherapy is a conventional treatment method for metastatic bone cancer, but it has limitations, such as lower drug-targeting of bone tissues and serious side effects. Bone metastasis almost always occurs in advanced cancer, and most patients in this period have strong drug resistance, which further worsens the curative effect. To address the above-mentioned difficulties, a drug delivery platform is proposed in this paper that accomplishes the bone-targeting of drugs to efficiently inhibit tumors. First, the anti-cancer drugs 5-fluorouracil (5-Fu) and indocyanine green (ICG) were loaded into a zeolitic imidazolate framework (ZIF-90) to form 5-Fu/ICG@ZIF-90. Polyethylene glycol with zoledronic acid (ZOL) was encapsulated using 5-Fu/ICG@ZIF-90 to synthesize 5-Fu/ICG@ZIF-90-PEG-ZOL nanoparticles, which showed dimensional stability, good thermal stability, and bone-targeting ability. Second, the in vitro anti-cancer activity of the designed platform was investigated using cytotoxicity, apoptosis, live–dead staining, cell cycle, and cell ultrathin section analysis. The results indicated that the nanoparticles inhibited MCF-7 cell activity when chemotherapy was combined with PTT. Finally, H&E staining and TUNEL detection were performed in mouse organs and tumors. The nanoparticles combined with photothermal therapy (PTT) and triggered by near-infrared irradiation induce apoptosis of tumor cells in vivo, displaying a better efficacy of combined chemotherapy and photothermal therapy. Experiments conducted on the 5-Fu/ICG@ZIF-90-PEG-ZOL nanoparticles demonstrated their promising performance for cancer bone metastasis inhibition.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Peng Luo,Yanlong Zhong,Xiaowei Yang,Qi Lai,Shaorong Huang,Xiaoyong Zhang,Bin Zhang,Yen Wei
Natural compounds have shown promising application prospects in preventing or treating various diseases, including osteoporosis on account of their abundant sources, low price, multi-targeting and multiple biological effects. As a bioactive natural product, quercetin (Que) has previously demonstrated to ameliorate osteoporosis (OP), however, its poor bioavailability resulting from low water solubility, poor stability and lack of bone-targeting largely restricted its efficacy and clinical applications. Inspired by the bone-targeting capability of phosphate compounds, we reported a one-step procedure for synthesis of phosphorylated Que (p-Que) by direct phosphorylating phenol groups of Que for the first time. The phosphate groups on p-Que could not only improve the water dispersibility of Que, but also endow p-Que desirable bioavailability and bone-targeting feature. The results from biological assays suggested that p-Que could inhibit osteoclastogenesis and bone resorption and alleviate trabeculae loss in osteoporotic mice. In conclusion, this work demonstrated that phosphorylation strategy can effectively solve low water solubility, lack of bone-targeting capability and poor bioavailability of natural compounds, providing a novel and efficient approach for development of OP nanomedicines.
研究领域:
药理学
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骨科学
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天然产物化学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2025
·
IF 7.9
Yanlong Zhong,Shaorong Huang,Peng Luo,Qi Lai,Fengbo Mo,Xinmin Yang,Xiaoyong Zhang,Bin Zhang,Yen Wei,Xiaowei Yang
Osteoporosis (OP) is a common metabolic disease, that mainly affects skeletal system with the features, including reduction bone density, deterioration bone structure, bone pain and increase risk of bone fracture. In this work, a well-known anti-osteoporosis natural compound named as dihydromyricetin (DMY) was selected as the model compound to construct a carrier-free bone targeting nanomedicine via a one-step phosphorylation reaction, in which the phenolic groups on DMY were converted into phosphate groups after reacting with phosphorus oxychloride. The resultant phosphorylated DMY (p-DMY) could self-assemble into nanoparticles with excellent water dispersibility and bone targeting capability because of the introduction of hydrophilic phosphate groups. In vitro results demonstrated p-DMY mainly inhibited osteoclast differentiation by blocking NF-κB and MAPK signals in a dose-dependent manner. More interestingly, p-DMY could significantly improve OP treatment efficacy in preventing bone loss and improving the biomechanics of bone tissues as compared with DMY in ovariectomy mice. Therefore, considered the facile synthesis procedure, enhanced OP treatment efficacy as well as negative toxicity of p-DMY, we trust this strategy described in this work should be an elegant tool for construction of natural compounds-based nanomedicines for OP and other metabolic disease treatment.
研究领域:
药理学
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生物医学工程
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代谢疾病研究
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DOI
高影响因子
ACS Nano
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2024
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IF 15.8
Yu Chen,Qi-Wen Chen,Fang-Sheng Fu,Hui-Yun Gu,Aixi Yu,Xian-Zheng Zhang
Therapeutic efficacy of skeletal diseases is usually limited by unfavorable drug delivery due to incapable bone targeting and low bone affinity of conventional drug carriers, as well as relatively reduced vascularization and dense structure of bone tissues. Due to CXC chemokine receptor 4 (CXCR4)/CXC chemokine ligand 12 (CXCL12) signal axis-guided recruitment, osteoprogenitor cells (OPCs) can actively migrate to bone disease nidus. Here, drugs-loaded nanoliposomes are prepared and decorated onto OPCs by biotin–streptavidin linkage for precise bone disease targeting and effective drug delivery. In mouse models of tibia defect and orthotopic osteosarcoma, superior targeting property of OPCs-based drug delivery systems toward diseased bone niduses is verified. By encapsulating antitumor and antiosteoporosis drugs into nanoliposomes, OPCs-based drug delivery systems effectively inhibit disease development and restore bone destruction in mouse models of orthotopic osteosarcoma and ovariectomized osteoporosis. This study reveals a cell-based drug delivery system for precise bone disease targeting and highly effective drug delivery, which will find great potential as a universal drug delivery platform for targeting treatment of various bone diseases.
研究领域:
医学
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药学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
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IF 4.9
Han Yan,Yuhao Liao,Weixiong Chen,Junnan Luo,Dongdong Li,Jilong Wang,Faxin Liu
Recently, osteoporosis has been a significant clinical challenge for the failed bone regeneration and vascularization. In this study, we developed a multifunctional nanoparticle system to stimulate bone regeneration and vascularization. Poly(D, L-lactide) (PLA)-based nanoparticles were fabricated to encapsulate icariin, which is renowned for its osteogenic potential. Subsequently, these nanoparticles were coated with red blood cell membranes to enhance biocompatibility. To further improve targeting specificity, a bone-targeted polymer-lipid consisting of alendronate-modified PEG-DSPE was synthesized and incorporated into the cell membrane coating. The delivery systems were designed to modulate bone marrow mesenchymal stem cells (BMSCs), thereby enhancing both osteogenesis and angiogenesis. Our findings demonstrate that the therapeutic system could enhance bone formation and vascularization in vitro , indicating its potential as an advanced treatment strategy for osteoporosis. This study provides a promising nanoplatform for the development of multifunctional nanomedicines aimed at improving bone health and vascular integration.
研究领域:
药学
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生物医学工程
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骨科学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2024
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IF 6.6
Demeng Xia,Qingqing Qian,Sheng Wang,Xiao Dong,Ying Liu
Introduction Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem.Methods Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments.Results In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice.Conclusion In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.
研究领域:
药理学
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骨生物学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2016
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IF 3.994
Weijing Chu,Yanjuan Huang,Chanzhen Yang,Yunhui Liao,Xuefei Zhang,Mina Yan,Shengmiao Cui,Chunshun Zhao
Because of the peculiarity of the bone microstructure, the uptake of chemotherapeutics often happens at non-targeted sites, which induces side effects. In order to solve this problem, we designed a bone-targeting drug delivery system that can release drug exclusively in the nidus of the bone. Alendronate (ALN), which has a high ability to target to hydroxyapatite , was used to fabricate double ALN-conjugated poly (ethylene glycol) 2000 material (ALN-PEG 2k -ALN). The ALN-PEG 2k -ALN was characterized using 1 H NMR and 31 P NMR and FTIR. ALN-PEG 2k -ALN-modified calcium phosphate nanoparticles (APA-CPNPs) with an ALN targeting moiety and hydrophilic poly (ethylene glycol) arms tiled on the surface was prepared for bone-targeted drug delivery. The distribution of ALN-PEG 2k -ALN was tested by X-ray photoelectron spectroscopy. Isothermal titration calorimetry data indicated that similar to free ALN, both ALN-PEG 2k -ALN and APA-CPNPs can bind to calcium ions. The bone-binding ability of APA-CPNPs was verified via ex vivo imaging of bone fragments. An in vitro release experiment demonstrated that APA-CPNPs can release drug faster in an acid environment than a neutral environment. Cell viability experiments indicated that blank APA-CPNPs possessed excellent biocompatibility with normal cells. Methotrexate (MTX) loaded APA-CPNPs have the same ability to inhibit cancer cells as free drug at high concentrations, while they are slightly weaker at low concentrations. All of these experiments verified the prospective application of APA-CPNPs as a bone-targeting drug delivery system.
研究领域:
药学
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生物医学工程
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2025
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IF 5.4
Xiaoxiong Jin,Wanying Wang,Hui Liu,Jing Zhao,Pengfei Li,Aoting Li,Ziyuan Song
Poly(l-glutamic acid)s (PLGs) are promising bone-targeting ligands due to their high molecular weight and facile preparation. Nevertheless, the bone-targeting efficiency of PLGs is still relatively low, validating the necessity to further enhance targeting through structural optimization. Herein, we report the use of a heteropolypeptide strategy to improve the bone targeting of PLGs through the incorporation of another side-chain functionality for enhanced affinity with bone tissues. Specifically, the introduction of cationic amino or aromatic phenolic side-chain residues resulted in a ∼2.3-fold or ∼1.6-fold increase in the in vivo bone targeting, respectively. Cationic modification not only improved the affinity with bone minerals but also exhibited prolonged retention in the bone tissues for more than 60 days. This work highlights the use of a heteropolypeptide library to screen and optimize the performance of polypeptide materials, offering promising bone-targeting polymeric materials for the design of bone-related nanomedicine.
研究领域:
生物材料学
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药剂学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of the Mechanical Behavior of Biomedical Materials
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2023
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IF 3.9
Wanzhen Li,Yongqi Yang,Jun Wang,Ting Ge,Shuixia Wan,Lin Gui,Yugui Tao,Ping Song,Liangjun Yang,Fei Ge,Weiwei Zhang
At present, simple anti-tumor drugs are ineffective at targeting bone tissue and are not purposed to treat patients with bone metastasis. In this study, zoledronic acid (ZOL) demonstrated excellent bone-targeting properties as a bone-targeting ligand. The metal-organic framework (MOF) known as ZIF-90 was modified with ZOL to construct a bone-targeting-based drug delivery system. Chlorin e6 (Ce6) was loaded in the bone-targeted drug delivery system and combined with 2-deoxy-D-glucose (2-DG), which successfully treated bone tumors when enhanced photodynamic therapy was applied. The Ce6@ZIF-PEG-ZOL (Ce6@ZPZ) nanoparticles were observed to have uniform morphology, a particle size of approximately 210 nm, and a potential of approximately −30.4 mV. The results of the bone-targeting experiments showed that Ce6@ZPZ exhibited a superior bone-targeted effect when compared to Ce6@ZIF-90-PEG. The Ce6@ZPZ solution was subjected to 660 nm irradiation and the resulting production of reactive oxygen species increased over time, which could be further increased when Ce6@ZPZ was used in combination with 2-DG. Their combination had a stronger inhibitory capacity against tumor cells than either 2-DG or Ce6@ZPZ alone, increasing the rate of tumor cell apoptosis. The apoptosis rate caused by HGC-27 was 61.56% when 2-DG was combined with Ce6@ZPZ. In vivo results also showed that Ce6@ZPZ combined with 2-DG maximally inhibited tumor growth and prolonged mice survival compared to the other experimental groups. Therefore, the combination of PDT and glycolytic inhibitors serves as a potential option for the treatment of cancer.
研究领域:
药学
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
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2015
·
IF 2.59
Wei-Liang Ye,Yi-Pu Zhao,Ren Na,Fei Li,Qi-Bing Mei,Ming-Gao Zhao,Si-Yuan Zhou
ABSTRACT Alendronate-monoethyl adipate-(hydrazone)-doxorubicin conjugate (ALN-MA-hyd-DOX) was synthesized to specifically deliver doxorubicin (DOX) to bone tumor tissue. The binding kinetics of ALN-MA-hyd-DOX with hydroxyapatite (HA) and natural bone were detected by using spectrophotometer. Cytotoxicity of ALN-MA-hyd-DOX on tumor cells was determined by MTT [3-(4,5-dimethylthiaol-2-yl)-2,5-diphenyl-tetrazolium bromide] method. The cellular uptake of ALN-MA-hyd-DOX was observed by using fluorescence microscopy . The in vivo antitumor activity of ALN-MA-hyd-DOX was investigated by using tumor-bearing nude mice model. The results indicated that ALN-MA-hyd-DOX was able to quickly bind with HA and natural bone. ALN-MA-hyd-DOX immobilized on the natural bone released more DOX in pH 5.0 medium than that in pH 6.0 or 7.4 medium. The cytotoxicity of ALN-MA-hyd-DOX toward A549 cells and MDA-MB-231/ADR cells was greater than DOX. ALN-MA-hyd-DOX was rapidly uptaken by A549 cells and MDA-MB-231/ADR cells. Compared with the same dose of free DOX, ALN-MA-hyd-DOX significantly decreased tumor volume of tumor-bearing nude mice. DOX mainly distributed in bone tumor tissue after ALN-MA-hyd-DOX was intravenously administered to tumor-bearing nude mice, whereas DOX distributed through the whole body after DOX was intravenously administered to tumor-bearing nude mice. These findings implied that the ALN-MA-hyd-DOX was a promising bone-targeted conjugate for treating bone neoplasms.
研究领域:
药理学
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肿瘤学
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
·
IF 5.2
Huilian Huang,Sajid Asghar,Ling Lin,Su Chen,Chenjun Yuan,Muhui Sang,Yanyu Xiao
The combination of chemotherapy and photothermal therapy not only improves the therapeutic effect but also limits the side effects of drugs. Herein, a multi-responsive dual-modality bone-targeted drug delivery vehicle for the treatment of osteosarcoma was designed by utilizing alendronate sodium as a bone-targeting ligand for the targeted delivery of doxorubicin (DOX) loaded polydopamine nanoparticles (PDA NPs) coated with γ-polyglutamic acid (APC@PDA/DOX NPs). The average size of spherical NPs was 140.0 nm with a zeta potential of −25.63 mV. The drug loading and encapsulation efficiency were 11.63 % and 96.44 %, respectively. The constructed NPs were responsive to acidic pH, redox conditions, and near-infrared light as the drug release rate of the system reached 70 %. Cell experiments showed that APC@PDA/DOX NPs significantly enhanced cytotoxicity in mouse K7M2 osteosarcoma cells due to PDA-induced hyperthermia and DOX-induced cytotoxicity. Compared with the free DOX solution, the area under the curve of APC@PDA/DOX NPs increased by 8.52 times, iterating the significantly prolonged circulation time of NPs in vivo that manifested in higher bioavailability. The biodistribution study showed that APC@PDA/DOX NPs enacted excellent bone targeting and tumor tissue localization. In general, APC@PDA/DOX NPs may offer a feasible and effective strategy for osteosarcoma-targeted therapy.
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Bowen Duan,Hongting Liu,Xiaoxuan Ji,Jingwen Dong,Xinping Luo,Feiran Zhang,Minjie Sun,Zhanwei Zhou
Osteosarcoma is one of the commonest malignant bone tumors in children and adolescents, and its preferred treatment is chemotherapy. However, the lack of sufficient blood vessels in the bone tissue and the dense collagen fibers in osteosarcoma severely weaken the drug-directional accumulation effect and intra-tumoral penetration, leading to poor therapeutic efficacy. Herein, we reported a bone-targeted permeable nanomicelle (Co1-PTX@DSAA) composed of aspartic acid (Asp)-modified dextran (DSAA) to deliver paclitaxel (PTX) and collagenase 1 (Co1) simultaneously for highly effective osteosarcoma treatment. The prepared nanomicelle possessed excellent osteosarcoma targeting ability as Asp can combine with hydroxyapatite (HAP) in bone. More intelligently, the surface-absorbed Co1 endowed PTX@DSAA with a special function like a nano-icebreaker, which could quickly destroy the collagen fibers to promote PTX penetration deeply in the tumor. Our work suggests that Co1-PTX@DSAA nanomicelles could quickly combine with HAP and Ca 2+ at an adsorption rate of ∼ 60% and ∼ 32%, respectively. Meanwhile, the penetration depth of Co1-PTX@DSAA could even reach 70 μm in the multicellular spheroids (MCSs) model. The tumor treatment efficiency of Co1-PTX@DSAA is 1.51 times that of free PTX. Overall, this unprecedented nanomicelle can simultaneously facilitate drug accumulation and deep penetration in the tumor, which will provide a promising strategy for future safe and high-efficiency clinical osteosarcoma treatment.
研究领域:
肿瘤学
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药学
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纳米技术
✓ 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）