INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Xulong Zhu,Shuhan Wu,Kuan Yang,Wei Wei,Yasir Aziz,Wenjin Yuan,Hideyuki Miyatake,Yoshihiro Ito,Zhao Wei,Jianhui Li,Yong Mei Chen
The fabrication of scaffolds capable of the sustained release of the vascular endothelial growth factor (VEGF) to promote angiogenesis in long time remains a challenge in tissue engineering. Here, we report a facile approach for effectively fabricating a bioactive scaffold that gradually releases VEGF to promote angiogenesis. The scaffold was fabricated by coating polydopamine (PDA) on a konjac glucomannan (KGM) scaffold, followed by the surface immobilization of VEGF with PDA. The resulting VEGF-PDA/KGM scaffold, with a porous and interconnected microstructure (392 μm pore size with 84.80 porosity), combined the features of long-term biodegradability (10 weeks with 51 % degradation rate), excellent biocompatibility, and sustained VEGF release for up to 21 days. The bioactive VEGF-PDA/KGM scaffold exhibited multiple angiogenic activities over time, as confirmed by in vivo and in vitro experiments. For example, the scaffold significantly promoted the attachment and proliferation of human umbilical vein endothelial cells and the formation of vascular tubes in vitro . Moreover, the in vivo results demonstrated the formation and maturation of blood vessels after subcutaneous implantation in rats for four weeks. This promising strategy is a feasible approach for producing bioactive materials that can induce angiogenesis in vivo . These findings provide a new avenue for designing and fabricating biocompatible and long-term biodegradable scaffolds for sustained VEGF release to facilitate angiogenesis.
研究领域:
组织工程
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生物材料
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生物医学工程
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促血管生成
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Jiaxin Liu,Shuang Li,Ge Li,Xiang Li,Changhui Yu,Zhijiang Fu,Xiangyu Li,Lesheng Teng,Youxin Li,Fengying Sun
Bevacizumab, a vascular endothelial growth factor (VEGF)-targeting drug, is widely used as an off-label therapeutic for age-related macular degeneration (AMD). To reduce the monthly administration frequency, this study investigated microspheres comprising a poly( d , l -lactide-co-glycolide)/poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PLGA/PCADK) blend that could be loaded with bevacizumab-dextran particles using solid-in-oil-in-water (S/O/W) emulsification. Control microspheres were also prepared through water-in-oil-in-water (W/O/W) emulsification. The structural stability of bevacizumab in the polymer monomers was analyzed using dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion chromatography (SEC-HPLC), circular dichroism (CD) and fluorescence spectroscopy. Subsequently, microspheres were prepared and evaluated in terms of their morphology, encapsulation efficiency and release behavior. PLGA/PCADK microspheres prepared by the S/O/W method with <20% PCADK showed a smooth spherical structure with a uniform distribution of bevacizumab. The microspheres exhibited a release behavior comprising a slight initial burst and an increasing total release over 50 days both in vitro and in vivo . Additionally, the microspheres were well tolerated by ocular tissue. Finally, a chorioallantoic membrane (CAM) assay revealed that the bioactivity of bevacizumab was retained by PCADK. In conclusion, these results suggest the potential for bevacizumab-loaded PLGA/PCADK microspheres prepared by the S/O/W method as a means of intravitreal therapy for ocular diseases.
研究领域:
药物学
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眼科学
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药物递送系统
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Qian Zhou,Haifei Kang,Monika Bielec,Xiaopei Wu,Qiao Cheng,Wenying Wei,Honglian Dai
Hydrogels are widely used as debriding agents on account of providing a moist environment for wound healing, however the lack of mechanical strength, angiogenesis and antibacterial property limits their applications. In this study, we synthesized novel divalent ion cross-liking hydrogels (copper, zinc, strontium and calcium) and compared the mechanical performance, swelling ratio, antibacterial properties and biocompatibility in vitro and vivo . Thereinto, among the four divalent ions cross-linked hydrogels, copper ion crosslinking exhibited the maximum breaking strength, while strontium and zinc ion cross-linked hydrogels exhibited an excellent mechanical strength. In addition, the swelling ratio and pore size of no-ion cross-linked hydrogels was larger than ion cross-kinked hydrogels. In vitro , the improvements on wound healing after hydrogel application were evaluated by histological and molecular assays by detecting VEGF and TGF-β expression. In vitro and in vivo study results showed that zinc cross-kinked hydrogel had a spectrum of antibacterial activities, cell viability, mechanical strength and the ability of wound closure by promoting fibroblasts migration, vascularization, collagen deposition and the formation of granulation tissue.
研究领域:
材料科学
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生物材料
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生物医学工程
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药理学
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2021
·Vol. 12
·期 1
·1-16
·
IF 6.832
Zhang Xinxin,Jiang Xiaorui,Jiang Shan,Cai Xiyu,Yu Shengji,Pei Guoxian
Background Tissue-engineered bone grafts (TEBGs) that undergo vascularization and neurotization evolve into functioning bone tissue. Previously, we verified that implanting sensory nerve tracts into TEBGs promoted osteogenesis. However, the precise mechanisms and interaction between seed cells were not explored. In this study, we hypothesized that neurotization may influence the osteogenesis of TEBGs through vascularization. Methods We cultured rat Schwann cells (SCs), aortic endothelial cells (AECs), and bone marrow-derived mesenchymal stem cells (BM-MSCs) and then obtained BM-MSC-derived induced endothelial cells (IECs) and induced osteoblasts (IOBs). IECs and AECs were cultured in an SC-conditioned medium (SC-CM) to assess proliferation, migration, capillary-like tube formation, and angiogenesis, and the vascular endothelial growth factor (VEGF) levels in the supernatants were detected. We established an indirect coculture model to detect the expression of nestin and VEGF receptors in IECs and tissue inhibitor of metalloproteinase (TIMP)-2 in SCs. Then, SCs, IECs, and IOBs were labeled and loaded into a β-tricalcium phosphate scaffold to induce prevascularization, and the scaffold was implanted into a 6-mm-long defect of rat femurs. Three groups were set up according to the loaded cells: I, SCs, and IECs (coculture for 3 days) plus IOBs; II, IECs (culture for 3 days) plus IOBs; III, IOBs. Nestin and TIMP-2 expression and osteogenesis of TEBGs were evaluated at 12 weeks post-implantation through histological and radiological assessments. Results We found that SC-CM promoted IEC proliferation, migration, capillary-like tube formation, and angiogenesis, but no similar effects were observed for AECs. IECs expressed nestin extensively, while AECs barely expressed nestin, and SC-CM promoted the VEGF secretion of IECs. In the coculture model, SCs promoted nestin and VEGF receptor expression in IECs, and IECs inhibited TIMP-2 expression in SCs. The promotion of prevascularized TEBGs by SCs and IECs in group I augmented new bone formation at 6 and 12 weeks. Nestin expression was higher in group I than in the other groups, while TIMP-2 expression was lower at 12 weeks. Conclusions This study demonstrated that SCs can promote TEBG osteogenesis via IECs and further revealed the related specific characteristics of IECs, providing preliminary cytological evidence for neurotization of TEBGs.
研究领域:
组织工程
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再生医学
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细胞生物学
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骨再生
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血管化
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产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2022
·Vol. 8
·期 2
·e10414
·
IF 10.684
Peng Luo,Jiarui Fang,Dazhi Yang,Lan Yu,Houqing Chen,Changging Jiang,Rui Guo,Tao Zhu,Shuo Tang
Bone injury caused changes to surrounding tissues, leading to a large number of osteoclasts appeared to clear the damaged bone tissue before bone regeneration. However, overactive osteoclasts will inhibit bone formation. In this study, we prepared methacrylylated gelatin (GelMA)-based hydrogel to co-crosslink with OP3-4 peptide, a receptor activator of NF-κB ligand (RANKL) binding agent, to achieve the slow release of OP3-4 peptide to inhibit the activation of osteoclasts, thus preventing the long-term existence of osteoclasts from affecting bone regeneration, and promoting osteogenic differentiation. Moreover, CXCL9 secreted by osteoblasts will bind to endogenous VEGF and inhibit vascularization, finally hinder bone formation. Thus, anti-CXCL9 antibodies (A-CXCL9) were also loaded in the hydrogel to neutralize excess CXCL9. The hydrogel slow released of OP3-4 cyclic peptide and A-CXCL9 to simultaneously inhibiting osteoclast activation and promoting vascularization, thereby accelerating the healing of femur defect. Further analysis of osteogenic protein expression and signal pathways showed that the hydrogel may be through activating the AKT-RUNX2-ALP pathway and ultimately promote osteogenic differentiation. This dual-acting hydrogel can effectively prevent nonunion caused by low vascularization and provide long-term support for the treatment of bone injury.
研究领域:
生物医学工程
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骨科
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再生医学
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药剂学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYPERTHERMIA
·
2024
·
IF 3
Yijin Fan,Xi Wang,Yao Liu,Huajun Tang,Chengzhi Li
Objective In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL).Materials and methods The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment.Results After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05).Conclusions These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.
研究领域:
肿瘤学
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妇科
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医学影像学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zhiwan Chen,Mengfei Yuan,Haojing Li,Lihua Li,Binghong Luo,Lu Lu,Qi Xiang,Shan Ding
The inflammation of chronic wounds plays a key hindering role in the wound healing process. Slowing down the inflammatory response is significant for the repair of chronic wounds. Studies have revealed that succinate can inactivate gastrin D (GSDMD) and prevent cell pyroptosis. Chitosan has anti-inflammatory properties and is commonly used as wound healing material. Therefore, we used succinic anhydride to modify chitosan and found that N-succinylated chitosan (NSC) was more effective in inhibiting inflammation. The results showed that the stimulation of TNF-α and high glucose induces overexpression of capase-1 and TNF-α in human umbilical vein endothelial cells (HUVEC), and down-expression of CD31. However, the expression of capase-1 and TNF-α decreased, while the expression of CD31, VEGF and IL-10 was up-regulated significantly in dysfunctional HUVEC cells after treated by NSC. Moreover, NSC can speed wound healing, histological examination results showed that wounds treated with NSC exhibited faster epithelial tissue regeneration and thicker collagen deposition. Overall, this study results suggested that NSC has the function of restoring the physiological functions of dysfunctional HUVEC cells induced by high glucose and TNF-α, and can accelerate wound healing, indicating that NSC has good potential to be applied in inflammatory chronic wounds such as diabetic foot.
研究领域:
药理学
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伤口愈合
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炎症
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细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
·
2024
·Vol. 50
·期 12
·2338-2345
·
IF 1.6
Yang Wang,Wenxin Liu,Hui Xu,Liyuan Dong,Yalou Jiao,Zhe Qiao
Objective Thin endometrium caused by various factors affects the conception rate of females worldwide; however, current medications are still insufficient. Therefore, a novel approach is needed. We previously reported the effect of menstrual blood-derived mesenchymal stem cells (MenSCs) in ameliorating ethanol-induced endometrial injuries. In the present study, we aimed to investigate whether the effect of MenSCs is enhanced by a combination of platelet-rich plasma (PRP) infusion. Methods An endometrial injury mouse model was established by infiltrating 95% ethanol for 15 s into the uterus, followed by MenSCs, PRP, or MenSCs + PRP treatment. Pathological changes were observed by HE staining. The expression of CK18, vimentin, ItgαVβ3, and VEGF was determined using IHC staining and WB blotting. Results Compared with the model, MenSCs, PRP, and MenSCs + PRP treatments significantly improved endometrial damage and thickness, with the combined therapy displaying the most pronounced efficacy. The density of CK18-, vimentin-, and ItgαVβ3 positive cells increased most significantly in the MenSCs + PRP group of mice. In addition, the protein expression of CK18, vimentin, and VEGF was significantly upregulated after MenSCs + PRP, MenSCs, and PRP treatment, with MenSCs + PRP therapy showing the best efficacy. Conclusion MenSCs + PRP therapy is more beneficial for ameliorating ethanol-induced endometrial damage than MenSCs or PRP alone, providing a basis for the investigation of novel approaches for treating thin endometria.
研究领域:
生殖医学
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干细胞生物学
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妇科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Hong Juncong,Wu Dongze,Wang Haitao,Gong Zhe,Zhu Xinxin,Chen Fang,Wang Zihang,Zhang Mingchen,Wang Xiumei,Fang Xiangqian,Yang Shuhui,Zhu Jinjin
Peripheral nerve injury is a debilitating condition that have a profound impact on the overall quality of an individual’s life. The repair of peripheral nerve defects continues to present significant challenges in the field. Iron oxide magnetic nanoparticles (IONPs) have been recognized as potent nanotools for promoting the regeneration of peripheral nerves due to their capability as biological carriers and their ability to template the hydrogel structure under an external magnetic field. This research used a fibrin nanofiber hydrogel loaded with IONPs (IONPs/fibrin) to promote the regeneration of peripheral nerves in rats. In vitro examination of PC12 cells on various concentrations of IONPs/fibrin hydrogels revealed a remarkable increase in NGF and VEGF expression at 2% IONPs concentration. The biocompatibility and degradation of 2% IONPs/fibrin hydrogel were assessed using the in vivo imaging system (IVIS), demonstrating subcutaneous degradation within a week without immediate inflammation. Bridging a 10-mm sciatic nerve gap in Sprague-Dawley rats with 2% IONPs/fibrin hydrogel led to satisfactory morphological recovery of myelinated nerve fibers. And motor functional recovery in the 2% IONPs/fibrin group was comparable to autografts at 6, 9, and 12 weeks postoperatively. Hence, the composite fibrin hydrogel incorporating 2% IONPs exhibits potential for peripheral nerve regeneration.
研究领域:
神经科学
·
生物材料
·
组织工程
·
再生医学
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2019
·
IF 6.944
Ziting Qian,Jiayuan Fei,Shenfei Zong,Kuo Yang,Lang Li,Ruiyang Liu,Zhuyuan Wang,Yiping Cui
A multifunctional microfluidic platform was demonstrated to monitor the interaction between tumor cells and endothelial cells by integrating a three-dimensional (3D) cell culture unit with a protein detection unit. In such a chip, breast cancer cells MCF7 were seeded into the collagen to form a 3D tumor environment while human umbilical vein endothelial cells (HUVECs) are seeded in the channel next to the collagen matrix. Thus, an in situ growth of angiogenic sprouting can be visualized through fluorescence in the 3D collagen matrix after a coculture of MCF7 and HUVEC after 4 days, which cannot be observed in the 2D culture environment. On the other hand, gold@silver core–shell nanorods were used as surface-enhanced Raman scattering (SERS) immunoprobes for the detection of the secretion of cytokine (vascular endothelial growth factor, VEGF). The limit of detection of the VEGF is 100 pg/mL. Further, as LiCl and bevacizumab can act as a promoter and an inhibitor of VEGF, the dynamic change of the concentration of VEGF under the stimulation of them was monitored by SERS signals. Thus, this integrated SERS microfluidic platform creates opportunity for the fundamental research of interaction between tumors and endothelial cells.
研究领域:
生物医学工程
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癌症研究
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微流控技术
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表面增强拉曼散射(SERS)
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Yu Wang,Lingyu Sun,Guopu Chen,Hanxu Chen,Yuanjin Zhao
Ionic hydrogels have attracted extensive attention because of their wide applicability in electronic skins, biosensors, and other biomedical areas. Tremendous effort is dedicated to developing ionic hydrogels with improved detection accuracy and multifunctionality. Herein, we present an inverse opal scaffold-based structural color ionic hydrogel with the desired features as intelligent patches for wound management. The patches were composed of a polyacrylamide-poly(vinyl alcohol)-polyethylenimine-lithium chloride (PAM–PVA-PEI-LiCl) inverse opal scaffold and a vascular endothelial growth factor (VEGF) mixed methacrylated gelatin (GelMA) hydrogel filler surface. The scaffold imparted the composite patches with brilliant structural color, conductive property, and freezing resistance, while the VEGF-GelMA surface could not only prevent the ionic hydrogel from the interference of complex wound conditions but also contribute to the cell proliferation and tissue repair in the wounds. Thus, the hydrogel patches could serve as electronic skins for in vivo wound healing and monitoring with high accuracy and reliability. These features indicate that the proposed structural color ionic hydrogel patches have great potential for clinical applications.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
伤口愈合
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Yongwei Hao,Cuixia Zheng,Lei Wang,Jinjie Zhang,Xiuxiu Niu,Qingling Song,Qianhua Feng,Hongjuan Zhao,Li Li,Hongling Zhang,Zhenzhong Zhang,Yun Zhang
Amorphous biodegradable metal phosphate nanomaterials are considered to possess great potential in cancer theranostic application due to their promise in providing ultra-sensitive pH-responsive therapeutic benefits and diagnostic functions simultaneously. Here we report the synthesis of photosensitising and acriflavine-carrying amorphous porous manganese phosphate (PMP) nanoparticles with ultra-sensitive pH-responsive degradability and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway . Carboxymethyl dextran (CMD) is chemically anchored on the surface of porous manganese phosphate theranostic system through the pH-responsive boronate esters. Upon the stimulus of the tumor acid microenvironment, manganese phosphate disintegrates and releases Mn 2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. Meanwhile, the released photosensitizer chlorin e6 (Ce6) produces ROS under irradiation while acriflavine (ACF) inhibits the HIF-1α/VEGF pathway during the burst release of VEGF in tumour induced by photodynamic therapy (PDT), resulting in increased therapeutic efficacy. Considering the strong pH responsivity, MRI signal amplification and drug release profile, the PMP nanoparticles offer new prospects for tumor acidity-activatable theranostic application by amplifying the PDT through inhibiting the HIF-1α /VEGF pathway timely while enhancing the MRI effect. Statement of Significance In this study, we report the synthesis of the tumor acidity-activatable amorphous porous manganese phosphate nanoparticles and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF-1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway. Besides, upon the stimulus of the tumor acid microenvironment, the manganese phosphate nanoparticles finally disintegrate and release Mn 2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. This nanoplatform is featured with distinctive advantages such as ultra pH-responsive drug release, MRI function and rational drug combination exploiting the blockage of the treatment escape signalling pathway.
研究领域:
癌症治疗
·
纳米技术
·
分子成像
·
生物医学工程
✓ 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）