Advanced Science
·
2025
·
IF 14.1
Xinyu Xu,Hao Wang,Xiaohan Mei,Dapeng Zeng,Zehao Yu,Shibo Liu,Ruiyan Li,Yanguo Qin
Malignant bone tumor defects are difficult to treat because of the simultaneous need for tumor treatment and bone-repair promotion. This study presents a bioactive composite scaffold (T-rGO@Au) for personalized bone defect repair and bone tumor treatment. The T-rGO@Au scaffold has a porous structure, and its mechanical properties are close to those of human cancellous bone. The T-rGO@Au scaffold can induce upregulation of osteopontin (OPN), RUNX-2, and osteocalcin (OCN) gene expression. In vivo experiments showed that the bone volume/total volume (BV/TV) ratio with the T-rGO@Au scaffold was the highest. The new bone was tightly integrated with the implant, demonstrating effective osseointegration. The T-rGO@Au scaffold locally generated high temperatures and reactive oxygen species under near-infrared excitation, and AuNPs enhanced the photothermal performance of rGO through the “antenna effect.” Furthermore, in vitro experiments showed that the tumor cell nuclei were destroyed, late-stage apoptotic cells increased, and cell morphology was severely damaged. Additionally, RNA-seq revealed that tumor cell destruction was mediated through signaling pathways, such as the MAPK pathway. In vivo antitumor experiments also demonstrated that the T-rGO@Au scaffold significantly inhibited the growth of tumor cells within 2 weeks. Thus, the T-rGO@Au scaffold provides a new treatment strategy for the development of implantable scaffolds for bone tumor defects.
研究领域:
生物医学工程
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2019
·
IF 8.013
Wentao Dang,Bing Ma,Zhiguang Huan,Rongcai Lin,Xiaoya Wang,Tian Li,JinFu Wu,Nan Ma,Haibo Zhu,Jiang Chang,Chengtie Wu
Bone tumors may lead to osteoporosis. It is of great significance to fabricate functional scaffolds for treating bone tumor, osteoporosis and repairing bone defects. In this study, LaB 6 micro-nanoparticles/poly( d , l -lactide)-modified β-tricalcium phosphate scaffolds (TCP-PDLLA-LB) were successfully prepared. The LaB 6 surface chemistry-reinforced TCP-PDLLA-LB scaffolds were endowed with the following excellent properties: (1) the enhanced mechanical strength. The TCP-PDLLA-5LB scaffolds possessed higher compression resistant capacity than TCP scaffolds owing to the strong adhesive property of PDLLA that bound the LaB 6 micro-nanoparticles and scaffolds tightly; (2) the excellent photothermal performance. TCP-PDLLA-LB scaffolds presented distinct photothermal property because of localized surface plasmon resonance effect of LaB 6 micro-nanoparticles when exposed to the near-infrared (NIR) light (wavelength: 808 nm) and it was flexibly controllable through changing the quantity of LaB 6 micro-nanoparticles, power density of NIR light and environmental humidity; (3) the excellent biological properties in vitro . When culturing with saos-2 bone tumor cells, the TCP-PDLLA-5LB scaffolds effectively killed the saos-2 cells through adjusting power density of NIR light, irradiation duration time of NIR light and irradiation times of NIR light. Additionally, the TCP-PDLLA-5LB scaffolds were able to release bioactive ions which were beneficial to the in vitro osteogenesis of rabbit bone marrow stromal cells (rBMSCs) by supporting the attachment and proliferation of rBMSCs as well as promoting the expressions of osteogenic genes BMP2, RUNX2 and COL 1; and (4) the abilities of effectively ablating bone tumors and supporting bone tissue regeneration in vivo . The bone tumor tissues were significantly ablated and suppressed through hyperthermia due to the existence of LaB 6 micro-nanoparticles on the scaffolds. Simultaneously, TCP-PDLLA-5LB scaffolds implanted in bone defects effectively helped new bone formation regardless of NIR light irradiation. In conclusion, LaB 6 surface chemistry-reinforced scaffolds possess the dual functions of ablating bone tumor and repairing bone defects, which offers a promising therapy strategy for tumor/disease-related bone tissue engineering.
研究领域:
生物医学工程
·
材料科学
·
肿瘤学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Mingming Wang,Xiaopan Cai,Jian Yang,Changping Wang,Lu Tong,Jianru Xiao,Lei Li
Bortezomib is a boronate proteasome inhibitor widely used as an efficient anticancer drug; however, the clinical use of bortezomib is hampered by its adverse effects such as hematotoxicity and peripheral neuropathy, and low efficacy on solid tumors due to unfavorable pharmacokinetics and poor penetration in the solid tumors. In this study, we developed a tripeptide Arg–Gly–Asp (RGD)-targeted dendrimer conjugated with catechol and poly(ethylene glycol) groups for the targeted delivery of bortezomib to metastatic bone tumors. Bortezomib was loaded on the dendrimer via a boronate–catechol linkage with pH-responsive property, which plays an essential role in the control of bortezomib loading and release. The nontargeted bortezomib nanomedicine showed minimal cytotoxicity at pH 7.4, but significantly increased anticancer activity when cyclic RGD (cRGD) moieties were anchored on the dendrimer surface. The ligand cRGD enabled efficient internalization of the bortezomib complex by breast cancer cells such as MDA-MB-231 cells. The targeted nanomedicine efficiently depressed the progression of metastatic bone tumors and significantly inhibited the tumor-associated osteolysis in a model of bone tumors. This study provided an insight into the development of nanomedicine for metastatic bone tumors.
研究领域:
药理学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2021
·
IF 3.512
Zhiyuan Meng,Yichao Liu,Kexiang Xu,Xing Sun,Qingwen Yu,Zhongqing Wu,Zheng Zhao
The simultaneous therapy of tumor recurrence and bone defects resulting from surgical resection of osteosarcoma is still a challenge in the clinic. Combination therapy based on a localized drug-delivery system shows great promise in the treatment of osteosarcoma. Herein, bifunctional polydopamine (PDA)-modified curcumin (CM)-loaded silk fibroin (SF) composite (SF/CM-PDA) nanofibrous scaffolds, which combined photothermal therapy with chemotherapy to synergistically enhance osteosarcoma therapy, were prepared by PDA coating of the SF/CM nanofibrous scaffolds fabricated by supercritical carbon dioxide (SC-CO2) technology. The PDA coating improved hydrophilicity and mechanical strength of the SF/CM scaffolds. The SF/CM-PDA scaffolds present good photothermal conversion capacity and excellent photostability. The low pH and near-infrared (NIR) irradiation could effectively accelerate release of CM in the SF/CM-PDA scaffolds. The in vitro anticancer results indicated that the biocompatible SF/CM-PDA scaffolds had a long-term, stable, and superior anticancer effect compared to pure CM. Furthermore, the SF/CM-PDA scaffolds significantly increased the growth inhibition of osteosarcoma MG-63 cells under NIR irradiation (808 nm and 1.3 W/cm2). Besides, the SF/CM-PDA scaffolds could enhance osteoblast MC3T3-E1 cell proliferation in vitro when the mass ratio of CM was 0.05–0.5%. This work has therefore demonstrated that the bifunctional SF/CM-PDA scaffolds provide a competitive strategy for local osteosarcoma therapy and bone regeneration.
研究领域:
生物材料学
·
肿瘤治疗学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2022
·
IF 8.663
Xin Wang,Dong Zhai,Xiaogang Yao,Yufeng Wang,Hongshi Ma,Xiaopeng Yu,Lin Du,Huixing Lin,Chengtie Wu
For therapy of tumor-induced bone defects, functional biomaterials with tumor therapy and bone regeneration are of great importance. In this study, 3D printing of calcium titanate (CaTiO 3 ) bioceramic scaffolds was prepared for the therapy of tumor-induced bone defects. The digital laser processing (DLP) based 3D printing technology was applied to prepared CaTiO 3 bioceramic scaffolds. It was found that the color of CaTiO 3 (CaTi) scaffolds was deeper with the sintering temperature rising. Interestingly, CaTi scaffolds with pink color were found with optimal compressive strength (13.44 ± 0.99 MPa) and satisfactory photothermal property when exposed to NIR laser. The temperature of pink CaTi scaffolds could be over 70 ℃ under NIR laser irradiation (1.32 W/cm 2 ). Attributing to such excellent photothermal performance, CaTi scaffolds had been used as a photothermal biomaterial for the effective therapy of the in vitro and in vivo bone tumor. Moreover, the prepared pink CaTi scaffolds possessed bone-forming in vitro and in vivo . Therefore, 3D printing of pink CaTi bioceramic scaffolds represents a promising strategy by using the bifunctional biomaterial for tumor-induced bone defect therapy.
研究领域:
生物医学工程
·
组织工程
·
材料科学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Shangsi Chen,Yue Wang,Xin Zhang,Jun Ma,Min Wang
Many biomaterials are made and studied to provide anticancer therapy, and many other biomaterials have been developed to assist body tissue regeneration . It has been a challenge to design and produce effective multifunctional, or bifunctional, biomaterials for clinical applications to prevent cancer recurrence and, at the same time, to promote new tissue formation after surgical removal of the tumor for millions of cancer patients. In this study, bifunctional UV and Sr 2+ double-crosslinked alginate (ALG)/allylated gelatin (GelAGE) hydrogels incorporated with polydopamine (PDA) particles were designed and made. Furthermore, doxorubicin hydrochloride (DOX), an anticancer drug , was incorporated in PDA particles. It was aimed for the new ALG/GelAGE-PDA@DOX hydrogels to exhibit anticancer synergy and hence provide combined chemotherapy and phototherapy (PTT) for bone tumor cell ablation . In vitro experiments using MG63 osteosarcoma cells showed that ALG/GelAGE-PDA@DOX hydrogels could effectively kill tumor cells through the synergy of controlled DOX release and hyperthermia ablation. It was also aimed for the new hydrogels to facilitate bone tissue regeneration at the original bone tumor site. The results of in vitro experiments demonstrated that owing to the release of Sr 2+ , the new hydrogels could promote the proliferation of rat bone mesenchymal stem cells (rBMSCs) and also the alkaline phosphatase (ALP) activity of cells, indicating their osteogenic promotion ability. The ALG/GelAGE-PDA@DOX hydrogels have therefore exhibited great potential for the treatment of bone tumor-related defects.
研究领域:
生物材料学
·
肿瘤治疗学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine
·
2024
·
IF 4.7
Yumei Wang,Yue Zhou,Dongliang Zhai,Hao Deng,Xiaoliang Chen
Aim: Nano-hydroxyapatite (nHA) is a good nanocarrier to load 223Ra, but the low specific activity (sp.act.) of 223Ra@nHA limits its application in medicine. Methods: We proposed a method for preparing nHA using PEG as a template, which significantly increases the sp.act of 223Ra@nHA and a new method to loaded 99mTc for in vivo tracking. Results: The nHA synthesized using PEG as a template was associated with higher sp.act for 223Ra in comparison to nHA with identical particle size and without PEG. The nHA load 99mTc-MDP was associated with higher labeling rate and stability in comparison to 99mTc. Conclusion: All these findings suggest that using PEG as a template and 99mTc-MDP could be the most effective of synthetic 223Ra/99mTc@nHA.
研究领域:
纳米技术
·
放射药学
·
癌症治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Yaqin Liu,Tao Li,Hongshi Ma,Dong Zhai,Cuijun Deng,Jinwu Wang,Shangjun Zhuo,Jiang Chang,Chengtie Wu
For treatment of bone tumor and regeneration of bone defects, the biomaterials should possess the ability to kill tumor cells and regenerate bone defect simultaneously. To date, there are a few biomaterials possessing such dual functions, the disadvantages, however, such as long-term toxicity and degradation, restrict their application. Although bioactive elements have been incorporated into biomaterials to improve their osteogenic activity, there is no report about elements-induced functional scaffolds for photothermal tumor therapy. Herein, the elements (Cu, Fe, Mn, Co)-doped bioactive glass-ceramic (BGC) scaffolds with photothermal effect and osteogenic differentiation ability were prepared via 3D-printing method. Moreover, the photothermal anti-tumor effect and osteogenic activity of these scaffolds were systematically investigated. The prepared elements-doped scaffolds possessed excellent photothermal performance, which displayed a trend, 5Cu-BGC > 5Fe-BGC > 5Mn-BGC > 5Co-BGC, in this study. The final temperature of elements-doped scaffolds can be well controlled by altering the doping element categories, contents and laser power density. Additionally, the hyperthermia induced by 5Cu-BGC, 5Fe-BGC and 5Mn-BGC effectively killed tumor cells in vitro and inhibited tumor growth in vivo . More importantly, 5Fe-BGC and 5Mn-BGC scaffolds could promote rabbit bone mesenchymal stem cells (rBMSCs) adhesion, and the ionic products released from elements-doped scaffolds significantly stimulated the osteogenic differentiation of bone-forming cells. These results suggested that 5Fe-BGC and 5Mn-BGC scaffolds possessed promising potential for photothermal treatment of bone tumor and at the same time for stimulating bone regeneration , representing a smart strategy for the treatment of bone tumors by combining dual functional bioactive ions with tissue engineering scaffolds. Statement of Significance The major innovation of this study is that we fabricated the elements (Cu, Fe, Mn, Co)-doped bioactive scaffolds via 3D printing technique and found that they possess distinct photothermal performance and osteogenic differentiation ability. To the best of our knowledge, there is no report about elements-doped scaffolds for photothermal therapy of bone tumor. This is an important research advance by combining the photothermal effect and osteogenic differentiation activity of bioactive elements in the scaffold system for potential bone tumor therapy and bone reconstruction . We optimized the elements-doped scaffolds and found the photothermal effect of elements-doped scaffolds (5Cu-BGC, 5Fe-BGC, 5Mn-BGC) could effectively kill tumor cells in vivo . The photothermal performance of elements-doped scaffolds follows a trend: 5Cu-BGC > 5Fe-BGC > 5Mn-BGC > 5Co-BGC > BGC. Compared to traditional nano-sized photothermal agents, bioactive elements-induced functional scaffolds have better biosecurity and bioactivity. Furthermore, 5Fe-BGC and 5Mn-BGC scaffolds displayed excellent bone-forming activity by stimulating the osteogenic differentiation of bone-forming cells. The major significance of the study is that the elements-doped bioactive glass-ceramics (5Fe-BGC, 5Mn-BGC) have great potential to be used as bifunctional scaffolds for photothermal tumor therapy and bone regeneration, representing a smart strategy for the treatment of bone tumors by combining dual functional bioactive ions with tissue engineering scaffolds.
研究领域:
生物医学工程
·
组织工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 12
·5044-5053
·
IF 5.251
Zi-Fei Zhou,Tuan-Wei Sun,Yun-Hao Qin,Ying-Jie Zhu,Ying-Ying Jiang,Yang Zhang,Jun-Jian Liu,Jin Wu,Shi-Sheng He,Feng Chen
One-dimensional hydroxyapatite (HA) particularly mimics the structure of mineralized collagen fibrils and displays superior mechanical properties such as toughness. Herein, we report Se-doped HA/chitosan (Se-HA/CS) biopapers constructed with self-assembled Se-doped HA nanowires and chitosan. The Se-HA/CS biopapers with high flexibility and manufacturability can not only be further processed into arbitrary shapes by folding or using scissors but also display high performances in in vitro/vivo anti-bone tumor studies. The Se-HA/CS biopapers are more inclined to inhibit the growth of tumor cells (HCS 2/8 and SJSA cells) than that of normal human bone marrow stromal cells (hBMSCs). The potential mechanisms of this meaningful anti-tumor effect were investigated, such as reactive oxygen species accumulation and the activation of apoptosis and the underlying signal pathway involved (including caspase family, Bcl-2 family and JNK/STAT3). The results demonstrate that Se-HA/CS biopapers may inhibit the growth of HCS 2/8 and SJSA cells by synchronously inducing JNK activation and STAT3 inhibition and consequently promote the apoptosis of these cells. Furthermore, the in vivo anti-tumor studies confirm that the Se-HA/CS biopapers obviously suppress the growth of patient-derived xenograft tumor models.
研究领域:
材料科学
·
生物材料
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Chemistry
·
2022
·
IF 7.613
Y. Pan,K. Huang,Y. Li,Y. Liu,H. Yu,Z. lv,R. Zou,Q. Yao
Removal of residual tumor cells and regeneration of large bone defects are urgently required after surgical resection of bone tumors. To address these issues, a bifunctional scaffold with high photothermal effect and osteogenesis was developed for bone tumor therapy. Sintered mesoporous imidazolate framework 8 (ZIF8) nanoparticles with porphyrin-like macrocycles were synthesized by calcination of ZIF8 precursors under an N 2 atmosphere. The prepared ZIF8 possesses good photothermal efficacy and drug loading capability. Phenamil (Phe), an activator of bone morphogenetic protein pathways, was encapsulated into ZIF8 before loading onto gelatin nanofibrous (GF) scaffolds. The loaded Phe exhibited sustained and near-infrared triggered release profiles, which is capable of promoting bone morphogenetic protein 2 induced osteogenic differentiation even under near-infrared treatment. Moreover, our studies revealed that the photothermal effect of GF/ZIF8-Phe scaffolds can kill MG-63 cells in vitro and inhibit subcutaneous tumor growth in vivo . Therefore, the GF/ZIF8-Phe scaffold represents a novel bifunctional platform for tumor therapy and bone regeneration.
研究领域:
生物材料学
·
医学
·
纳米医学
✓ 已验证
DOI
高影响因子
DRUG DELIVERY
·
2023
·
IF 6
Dongliang Zhai,Yumei Wang,Songke Yu,Jiren Zhou,Jia Song,Shilei Hao,Xiaoliang Chen
The clinical diagnosis and treatment of malignant bone tumors are still major clinical challenges due to their high incidence are difficulty. Targeted therapies have become a critical approach to treat bone tumors. In recent years, radiopharmaceuticals have been used widely and have shown potent and efficient results in treating bone tumors, among which 32P and the labeled radiopharmaceuticals play an essential role. In this study, the 32P-labeled hydroxyapatite (HA) was prepared through chemical synthesis (32P-Hap) and physical adsorption (32P-doped-Hap). The in vitro stability of 32P-labeled HA was analyzed to assess the superiority of the new-found chemical synthesis. The radiolabeling yield and stability of chemical synthesis (97.6 ± 0.5%) were significantly improved compared with physical adsorption (92.7 ± 0.4%). Furthermore, the CT results corroborate that 32P-Hap (100 μCi) +DOX group has the highest tumor suppression rate and can effectively reduce bone destruction. The results corroborate the effectiveness of the chemical synthesis and validate the application of 32P-Hap in bone tumors. Therefore, 32P-Hap (100 μCi) + DOX may be an effective strategy for bone metastasis treatments.
研究领域:
医学
·
放射生物学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yaoxun Zeng,Jiongpeng Yuan,Zhili Ran,Xiaoguang Zhan,Xinyi Li,Huiling Ye,Jiapeng Dong,Guining Cao,Zhenxing Pan,Ying Bao,Junze Tang,Xujie Liu,Yan He
Surgical resection remains the primary treatment modality for bone tumors. However, it is prone to local bone defects and tumor recurrence. Therefore, there is an urgent need for multifunctional biomaterials that combine tumor treatment and bone repair after bone tumor surgery. Herein, a chitosan composite scaffold (CS/DOX@Ti-MOF) was designed for both tumor therapy and bone repair. Among them, the amino-functionalized Ti-based metal-organic framework (NH 2 -MIL-125 (Ti), Ti-MOF) has a high specific surface area of 1116 m 2 /g and excellent biocompatibility, and promotes osteogenic differentiation. The doxorubicin (DOX) loading capacity of Ti-MOF was 322 ± 21 mg/g, and DOX@Ti-MOF has perfect antitumor activity. Furthermore, the incorporation of DOX@Ti-MOF improved the physical and mechanical properties of the composite scaffolds, making the scaffold surface rough and favorable for cells to attach. CS/DOX@Ti-MOF retains the unique properties of each component. It responds to the release of DOX in the tumor microenvironment to remove residual tumor cells, followed by providing a site for cell attachment, proliferation, and differentiation. This promotes bone repair and achieves the sequential treatment of postoperative bone tumors. Overall, CS/DOX@Ti-MOF may be a promising substitute for postoperative bone tumor clearance and bone defect repair. It also provides a possible strategy for postoperative bone tumor treatment.
研究领域:
生物材料
·
组织工程
·
癌症治疗
·
骨科手术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）