ACS Applied Nano Materials
·
2026
·Vol. 9
·期 34
·16342-16355
·
IF 5.8
Zheng Cuixia,Li Chenchen,Zhang Xuguang,Duan Changchun,Bai Haixin,Hong Chen,Wang Lei,Liu Yang
Bone
metastasis is a major cause of mortality in patients with
advanced breast cancer, and its treatment remains highly challenging
because of the complex pathological microenvironment in bone tissue.
Herein, we developed a dual-targeting nanoplatform for the cascade
delivery of bisphosphonates and antitumor agents to synergistically
treat breast cancer bone metastasis. Following systemic administration,
zoledronic acid (ZOL)-functionalized nanoparticles Cu/ZIF@DL/SSZ-ZOL
exhibit specific accumulation at bone metastasis sites, achieving
drug delivery on the tissue level. Charge reversal of Cu/ZIF@DL/SSZ
at the bone resorption interface leads to the detachment of ZOL and
enhances the affinity of Cu/ZIF@DL/SSZ toward tumor cells, achieving
drug delivery at the cellular level. After internalization by tumor
cells, Cu/ZIF@DL/SSZ effectively suppress tumor cell proliferation
via apoptosis, ferroptosis, and cuproptosis. The combined effects
of ZOL-mediated inhibition of bone resorption and the Cu/ZIF@DL/SSZ-induced
tumor inhibition effect disrupt the vicious cycle between tumor progression
and bone destruction, resulting in potent antitumor efficacy. Consequently,
this dual-targeting theranostic nanoagent achieves an effective treatment
of breast cancer bone metastasis in animal models. Overall, this dual-targeting
theranostic nanoagent offers a promising therapeutic strategy for
the treatment of breast cancer bone metastases.
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Journal of the Mechanical Behavior of Biomedical Materials
·
2023
·
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.
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Biomaterials Science
·
2022
·Vol. 10
·期 7
·1831-1843
·
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.
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TISSUE & CELL
·
2023
·
IF 2.6
Yao Duan,Chanyuan Jin,Yuwei Wu,Yan Chen,Minjuan Zhang,Jun Qian,Ting Shuai,Jian Li,Huimin Chen,Dan Li
Periodontitis represents a severe inflammatory illness in tooth supporting tissue. It has been supported that cAMP response element binding protein 1 (CREB1), a common transcription factor, extensively participates in osteogenic differentiation. Here, the current study was to look into the impacts of CREB1 on the process of periodontitis and its possible action mechanism. After human periodontal ligament stem cells (PDLSCs) were challenged with zoledronic acid (ZA), CREB1 expression was examined with RT-qPCR and western blotting . CCK-8 assay appraised cell activity. Following CREB1 elevation or/and vascular endothelial growth factor (VEGF) silencing in ZA-treated PDLSCs, CCK-8 and TUNEL assays separately estimated cell viability and apoptosis. Western blotting tested the expression of apoptosis- and osteogenic differentiation-associated proteins. ALP staining measured PDLSCs osteogenic ability and ARS staining estimated mineralized nodule formation. JASPAR predicted the potential binding of CREB1 with VEGF promoter, which was then testified by ChIP and luciferase reporter assays. RT-qPCR and western blotting tested VEGF expression. CREB1 expression was declined in ZA-exposed PDLSCs and CREB1 elevation exacerbated the viability and osteogenic differentiation while obstructed the apoptosis of PDLSCs. Additionally, CREB1 bond to VEGF promoter and transcriptionally activated VEGF expression. Further, VEGF absence partially stimulated the apoptosis while suppressed the osteogenic differentiation of CREB1-overexpressing PDLSCs treated by ZA. To be concluded, CREB1 might activate VEGF transcription to obstruct the apoptosis while contribute to the osteogenic differentiation of ZA-treated PDLSCs.
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ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Xi Cui,Yizhu Shan,Jiaxuan Li,Meng Xiao,Yuan Xi,Jianying Ji,Engui Wang,Baokun Zhang,Lingling Xu,Mingzhu Zhang,Zhou Li,Yingzi Zhang
Prevention of aseptic loosening, the main reason for secondary surgery of bone implants, is of great crucial clinical importance. As a promising bioactive material to promote bone regeneration, the piezoelectric materials for preventing aseptic loosening has not been reported. Here, a surface coating is presented for implants based on piezoelectric poly(L-lactic acid) (PLLA). The coating ingeniously utilizes zoledronic acid (ZA), a drug used to treat osteoporosis, as a nucleating agent to enhance the piezoelectricity of PLLA. The coating can not only provide a continuous porous piezoelectric environment to stimulate osteogenic differentiation without intervention, but also effectively inhibit the osteolytic activity of osteoclasts through the slow release of ZA, achieving long-term effectiveness with a single implantation. The rat femur cavity implantation experiment suggests that, the PLLA/ZA coating can rapidly initiate osseointegration of the implant and effectively mitigate the risk of aseptic loosening, even in the presence of metal submicroscopic particles that induce aseptic loosening. This strategy of piezo-enhanced PLLA drug-loaded coating may provide a new idea for the surface modification of bone implants.
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Advanced Healthcare Materials
·
2024
·
IF 10
Dehui Fan,Jing Li,Luwei Li,Ming An,Hua Yang,Guoqiang Zhou,Shutao Gao,Massimo Bottini,Jinchao Zhang,Kun Ge
The treatment of breast cancer bone metastasis is an unresolved clinical challenge, mostly because currently therapeutic approaches cannot simultaneously block the tumor growth and repair the osteolytic bone injuries at the metastatic site. Herein, the study develops a novel nanomedicine to treat breast cancer bone metastasis. The nanomedicine is based on phosphate ion-responsive and calcium peroxide-based nanoparticles carrying the bone-targeting agent zoledronic acid on the surface and loaded with the photosensitizer indocyanine green. Following intravenous administration to a mouse model of breast cancer bone metastasis, the nanoparticles efficiently accumulate at the bone metastasis site, react with free phosphate ions, and form hydroxyapatite nanoaggregates and O 2 , while releasing the photosensitizer. Hydroxyapatite nanoaggregates elicit the remineralization of the collagenous bone matrix and trigger tumor cell apoptosis. Upon irradiating tumor-bearing legs with an 808 nm laser source, the O 2 and free photosensitizer produced 1 O 2 by the reaction of the nanoparticles with phosphate ions, further boosting the anti-tumor effect. Tumor killing hampers the vicious cycle at the site of bone metastasis, translating to osteolysis blockade and further encouraging the remineralization of bone matrix. This work sheds light on the development of a novel, safe, and efficient approach for the treatment of breast cancer bone metastasis.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Fuchao Chu,Zhenxin Wang,Dazhen Zhang,Wenkang Xu,Boyan Huang,Chen Long,Shuo Yang,Xinzhe Qu,Cunjiu Gao,Feng Yuan
Although titanium alloy is the most widely used endoplant material in orthopedics, the material is bioinert and good bone integration is difficult to achieve. Zoledronic acid (ZOL) has been shown to locally inhibit osteoclast formation and prevent osteoporosis, but excessive concentrations of ZOL exert an inhibitory effect on osteoblasts; therefore, stable and controlled local release of ZOL may reshape bone balance and promote bone regeneration. To promote the adhesion of osteoblasts to many polar groups, researchers have applied gelatine methacryloyl (Gelma) combined with polyacrylamide hydrogel (PAAM), which significantly increased the hydrogen bonding force between the samples and improved the stability of the coating and drug release. A series of experiments demonstrated that the Gelma/PAAM-ZOL bioactive coating on the surface of the titanium alloy was successfully prepared. The coating can induce osteoclast apoptosis, promote osteoblast proliferation and differentiation, achieve dual regulation of bone regeneration, successfully disrupt the balance of bone remodelling and promote bone tissue regeneration. Additionally, the coating improves the metal biological inertness on the surface of titanium alloys and improves the bone integration of the scaffold, offering a new strategy for bone tissue engineering to promote bone technology.
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ACS Nano
·
2025
·
IF 16
Wei Wang,Xing Zhang,Lichen Zhang,Ziang Li,Lingjun Wang,Xinzhao Jiang,Jie Wu,Liang Zhou,Qiangqiang Guo,Yiyang Huang,Wenbo Wang,Kun Xi,Gert Storm,Yong Gu,Liang Chen
Osteoporosis, which is characterized by reduced bone mass and structurally compromised bone tissue, along with aberrant levels of reactive oxygen species (ROS) and inflammation, has been a pressing clinical challenge. A large accumulation of ROS and pro-inflammatory factors can result in mitochondrial dysfunction and progressive cellular senescence, impeding efficacious regeneration of bone defects. Herein, in this work, a ROS-responsive hydrogel system containing HA-PBA coated Ce-ZOL nanocomposites (GHCZ) for excessive ROS scavenging and reversal of cellular senescence to accelerate bone regeneration in osteoporosis was designed and presented. The GHCZ hydrogel system allows for the sustained release of HA-PBA coated Ce-ZOL nanoparticles, which may scavenge the extracellular and intracellular ROS of BMSCs and macrophages through their prominent enzyme-like catalytic effect. Moreover, the GHCZ hydrogel system transforms the polarization phenotype of macrophages into anti-inflammation M2 type and inhibits pro-inflammatory cytokines. Meanwhile, it could reverse the senescence of BMSCs and apparently elevate their pro-osteogenic capacity through safeguarding mitochondrial function and reprograming the metabolic processes, ultimately promoting the healing of bone defects. Based on in vitro and in vivo results, powerful immunomodulation, favorable pro-inflammatory/oxidative microenvironment reshaping properties, desirable mitochondrial protection, and superior pro-osteogenic capacity of such a GHCZ hydrogel system display the profound effects on augmenting bone repair, which offers a paradigm for treating osteoporotic bone defects.
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-11
·
IF 15.7
Li Luyao,Wang Cheng,Chu Weicun,Park Jaewang,Dai Yiming,Ba Qiankai,Wang Kaifeng,Gao Jiaxing,Wei Zeliang,Zhao Xiaoming,Nie Xuchen,Yin Lixiong,Seok Sang Il,Nie Riming,Guo Wanlin
The interfacial modifications between perovskite and charge-transport layers can arise from strong chemisorption bonds or weak physical adsorption interactions. However, modifications based on physical adsorption are susceptible to detachment, which not only disrupts the original energy level alignment and defect passivation but also introduces new charge recombination centers. Here, we report a fully chemical modification strategy in which the interfacial modifiers undergo an in situ crosslinking-like reaction, forming a localized, chemically bonded layer that seamlessly extends from the bulk of the underlying transport layer to the interface. Perovskite solar cells (PSCs) fabricated with this fully chemical modification strategy achieve a power conversion efficiency (PCE) of 25.52% (certified 25.49%) under standard conditions, representing one of the highest PCEs reported for devices fully fabricated in an ambient atmosphere. In terms of static stability, unencapsulated devices exhibit linear extrapolated T 80 lifetimes of 27,000 h during dark shelf storage and 19,000 h under thermal stress at 85 °C, both of which are record-breaking values for dark shelf and thermal stability, respectively. For dynamic stability, the devices maintain a linear extrapolated T 80 lifetime of 2,600 h under light-dark cycling, representing the most dynamically stable PSCs reported to date.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Enyang Yao,Yang Li,Kai Deng,Wei He,Milad Ashrafizadeh,João Conde,Liyu Yang
Osteosarcoma is the most common primary bone tumor with a high metastatic rate. Despite the improvement in patient prognosis with conventional therapeutics, enhancing the survival of patients with metastatic disease remains a challenge. Zoledronic acid (ZOL) stimulates apoptosis in cancer cells and is considered a promising drug for osteosarcoma therapy. Moreover, depletion of Inhibin Subunit Beta A (INHBA), a member of the transforming growth factor superfamily, can suppress osteosarcoma cell proliferation and invasion. Regarding the restricted potential of monotherapy, combination therapies, such as small interfering RNA (siRNA) and chemotherapy, are ideal strategies. However, off-target effects and adverse impacts lead to unsatisfactory clinical efficacy of these drugs. To address this challenge, we designed a folic acid-modified macrophage membrane coated with a carbon quantum dot (CQD) nanoplatform for the co-delivery of ZOL and siINHBA (ZOL-siINHBA@CQD@RM-FA). The anticancer activity of this nanotherapeutic agent was examined in vitro and in vivo . ZOL-siINHBA@CQD@RM-FA was approximately 200.7 nm in size, had a negative charge, excellent pH responsiveness, desirable biocompatibility, and high cellular uptake. This nanosystem achieved favorable co-delivery of ZOL/siINHBA and impaired osteosarcoma proliferation and invasion in vitro . Notably, intravenous administration facilitated tumor growth regression and inhibited lung metastasis without systemic toxicity. Accordingly, this nanotherapy could be considered an effective treatment for osteosarcoma, and the nanodelivery system shows potential for combined therapy by co-delivering genes and chemotherapy drugs.
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Nature Communications
·
2025
·Vol. 16
·期 1
·10275
·
IF 15.7
Fu Xiaoxue,Luo Zhenyu,Guo Yuqi,Meng Weikun,Jin Shue,Chen Junyu,Cai Yongrui,Luo Zeyu,Huang Chao,Chen Anjing,Guo Siqin,Chen Maojia,Zhou Zongke,Zeng Weinan
Diabetes mellitus (DM) bone defects face impaired healing due to hyperglycemia, chronic inflammation, and dysregulated bone remodeling, yet existing therapies lack comprehensive strategies targeting these interconnected issues. Herein, a glucose/ROS-responsive multifunctional hydrogel (AAT-ZCG) is designed, integrating tannic acid (TA)-mediated dynamic borate ester bonds and a cascade nanozyme comprising cerium-zoledronic acid-glucose oxidase (ZCG). The hydrogel enables stimuli-responsive release of TA and ZCG within DM microenvironments, depleting glucose via glucose oxidase-mediated catalysis and mitigating inflammation through cerium-mediated ROS scavenging. Moreover, ZCG modulates macrophage polarization, stimulates angiogenesis and enhances osteogenesis. Acidic byproducts trigger ZCG degradation, releasing zoledronic acid to inhibit excessive osteoclast activation. Transcriptomic analysis reveals upregulated forkhead box O1 transcription factor, a key regulator of bone metabolism and inflammation. This platform concurrently addresses pivotal mediators in DM bone defects, overcoming limitations of single-target approaches. By consolidating multifunctional responses, AAT-ZCG provides a concise yet effective strategy for DM bone defect regeneration.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Min Zhang,Dehui Fan,Wenchang Wu,Lixin Feng,Tong Sun,Hua Yang,Guoqiang Zhou,Jinchao Zhang,Yu Han,Kun Ge
The clinical management of breast cancer bone metastasis presents a significant therapeutic challenge, primarily due to the inadequate delivery of drugs to the bone microenvironment. To address this issue, this study developed bone-targeting single-atom nanozymes aimed at the targeted treatment of breast cancer bone metastases. These nanozymes were synthesized using a coordination‑carbonation strategy and modified with zoledronic acid (ZOL) to enhance their bone-targeting properties. When administered intravenously in a murine model of breast cancer bone metastasis, they efficiently accumulated in bone tissue. Single-atom iron in the nanozymes efficiently catalyzed the production of hydroxyl radicals (•OH) from hydrogen peroxide (H 2 O 2 ) in the acidic microenvironment created by tumor and osteolysis. Under near-infrared region II (NIR-II) laser irradiation, the nanozymes exhibited mild photothermal properties that enhanced chemodynamic therapy (CDT). This combination resulted in effective tumor cell ablation while simultaneously suppressing osteoclast activity, differentiation, and maturation. The dual synergistic therapy of photothermal and CDT effectively inhibited pathological osteolysis while precisely targeting malignant cells, offering a promising strategy for treating breast cancer bone metastasis.
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