BIOMATERIALS
·
2019
·
IF 10.273
Yan Zhang,Lu Zhang,Zhenzhen Wang,Faming Wang,Lihua Kang,Fangfang Cao,Kai Dong,Jinsong Ren,Xiaogang Qu
Covalent organic frameworks (COFs) and their derivatives represent an emerging class of crystalline porous materials with broad potential applications. However, the biomedical applications of them were limited by the large size, low dispersivity, poor bioavailability within cells and metabolic problems. Herein, renal-clearable ultrasmall COF nanodots have been synthesized and utilized as efficient cancer therapy agents. A simple liquid exfoliation strategy was used to prepare COF nanodots. After polyethylene glycol (PEG) conjugation, the PEG coated COF nanodots (COF nanodots-PEG) showed improved physiological stability and biocompatibility. In addition, the well isolated porphyrin molecules endowed COF nanodots-PEG good light-triggered reactive oxygen species production ability, which showed excellent photodynamic therapy efficiency with good tumor accumulation ability. In particular, due to the ultrasmall size, COF nanodots-PEG could be cleared from the body through the renal filtration with no appreciable in vivo toxicity. Our study highlights the potential of COFs-based nanoparticles for biomedical applications.
研究领域:
生物医学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Jiangpeng Pan,Juntao Wang,Wei Wang,Ziyang Liu,Shuai Huo,Lei Yan,Wei Jiang,Fengmin Shao,Yue Gu
Mitochondrial dysfunction-induced oxidative stress is a key pathogenic factor in acute kidney injury (AKI). Despite this, current mitochondrial-targeted antioxidant therapies have shown limited efficacy in clinical settings. In this study, we introduce a novel renal-clearable and mitochondria-targeted antioxidant nanozyme (TPP@RuCDzyme) designed to precisely modulate mitochondrial oxidative stress and mitigate AKI progression. TPP@RuCDzyme was synthesized by integrating ruthenium-doped carbon dots (CDs) with triphenylphosphine (TPP), a mitochondria-targeting moiety. This nanozyme system exhibits cascade enzyme-like activities, mimicking superoxide dismutase (SOD) and catalase (CAT), to efficiently convert cytotoxic superoxide (O 2 • - ) and hydrogen peroxide (H 2 O 2 ) into non-toxic water (H 2 O) and oxygen (O 2 ). This dual-enzyme mimicry effectively alleviates mitochondrial oxidative damage, restores mitochondrial function, and inhibits apoptosis. Compared to RuCDzyme alone, TPP@RuCDzyme demonstrated significantly enhanced efficacy in alleviating glycerol-induced AKI by inhibiting oxidative stress. By leveraging the catalytic activity derived from the integration of CDs and a metallic element, this study presents a promising therapeutic strategy for AKI and other renal diseases associated with mitochondrial dysfunction.
研究领域:
生物医学工程
·
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY
·
2024
·
IF 4.3
Yong Jian,Gengshen Mo,Weiyuan Xu,Yao Liu,Zhichao Zhang,Yinghui Ding,Ruonan Gao,Jiao Xu,Jiang Zhu,Kun Shu,Zhihan Yan,Fabio Carniato,Carlos Platas-Iglesias,Fangfu Ye,Mauro Botta,Lixiong Dai
In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.
研究领域:
化学
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材料科学
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医学成像
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 40
·19052-19063
·
IF 7.233
Yanlei Liu,Xiao Zhi,Wenxiu Hou,Fangfang Xia,Jingpu Zhang,Lexiang Li,Yuping Hong,Hao Yan,Chen Peng,Jesus Martinez de la Fuentea,Jie Song,Daxiang Cui
The development of multifunctional nanoparticles for tumor theranostics has become a research hotspot. Despite the advantages of non-invasive precision diagnostics and efficient drug-delivery, these nanoparticles bring two significant issues: (i) a potential toxic effect and (ii) difficult clearance. To solve these issues, carbon dots (C-dots) are key potential candidates owing to their unique properties, such as excellent biocompatibility and rapid renal clearance. However, their small size leads to a short circulation time in the blood, which causes non-sufficient tumor accumulation for antitumor therapy. To reach the balance between an efficient accumulation in a tumor and rapid clearance from the body, herein we report a new multifunctional nanoprobe: photosensitizer (chlorine e6, Ce6)-loaded assembled C-dots (A-C-dots@Ce6). The A-C-dots@Ce6 were assembled from negatively-charged discrete C-dots using Gd3+ ions as a “glue”. which also provided another function of in vivo nanoprobe monitoring via magnetic resonance (MR) imaging. Moreover, the nanoprobe exhibited an acidic pH-dependent disassembly and drug-release property. Benefiting from these advantages, the nanoprobe showed a targeted antitumor effect in A549 tumor-bearing mice under laser irradiation and gradual disassembly in the tumor for later body clearance. Therefore, the nanoprobe potentially provides a new strategy to solve the above balance issue, and brightens the future for antitumor monitoring and treatment.
研究领域:
纳米技术
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生物医学工程
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药学
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材料科学
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医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2021
·
IF 4.889
Wen Zhang,Bo Li,Yuhan Zhu,Xin Yao,Xiaohe Tian,Shengli Li,Yupeng Tian,Dandan Li
It is considerably meaningful to fabricate a second near-infrared spectral region (NIR-II, 1000–1700 nm) responsive theranostic nanoplatform simultaneously possessing good stability and biocompatibility for efficient and safe cancer treatment. In this work, as a flexible strategy, an intelligent nanoplatform was prepared by using water-soluble cyclic oligosaccharides α-cyclodextrin (α-CD) to load photosensitizer Chlorin e6 (Ce6) onto Fe 3 O 4 @Cu 2−x S core−shell nanoparticles (NPs). The as-synthesized Fe 3 O 4 @Cu 2−x S-Ce6/α-CD NPs are ultrasmall (≈5 nm) and aqueously dispersible, which offer both biocompatibility and renal clearance. Resultly, the obtained Fe 3 O 4 @Cu 2−x S-Ce6/α-CD NPs feature remarkable absorption in the second near-infrared region (NIR-II), which can provide advantages of large penetration depth and high photothermal conversion efficiency (η = 67.88%). Additionally, the introduction of Ce6 can trigger the generation of 1 O 2 under visible light irradiation. Therefore, it provides the proof-of-concept application of functional materials in photodynamic and photothermal combination cancer therapy.
研究领域:
生物医学工程
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纳米技术
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癌症研究
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诊疗学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2016
·
IF 6.008
Zhoujiang Chen,Nan He,Maohua Chen,Long Zhao,Xiaohong Li
Micelles self-assembled from drug-conjugated polymers indicate advantages in alleviating the premature release before reaching the intended site. Hyaluronic acid (HA) is known to specifically bind with a transmembrane glycoprotein CD44 , overexpressed in many types of cancerous cells, and can also be served as micelle carriers. However, an excess amount of drug conjugation to HA backbone may be detrimental to the receptor-mediated cellular uptake. Up to now, the effect of conjugation densities of drugs has never been determined on the physical properties and biological performance of resulting micelles. In the current study, camptothecin (CPT) was conjugated on HA through 3,3′-dithiodipropionic acid to self-assemble into reduction-sensitive micelles. The substitution degrees of CPT on HA backbone were tuned from around 4–20%, to clarify the effects on the cellular uptake efficiency and cytotoxicities of micelles, as well as the tumor accumulation and antitumor efficacy. The CPT substitution degree of around 15% on HA resulted in micelles with a higher cytotoxicity to 4T1 cells and achieved a better balance between the cellular uptake and reduction-triggered drug release, compared with other micelles. In contrast to a fast kidney clearance and an even distribution in major organs after intravenous injection of free CPT, the optimized micelles were accumulated in tumors, livers and lungs. The micelle content indicated a significant decrease in livers after 24 h, while that in tumors displayed a significant increase to 4.9% of the injection dose. The tumor accumulation of micelles led to strong tumor suppression with minimal systemic toxicity. The in situ tumor inhibition and the accumulation of micelles in liver and lungs inhibited tumor metastasis to these tissues. It demonstrates a feasible strategy to develop drug-HA conjugate micelles with a concise and tunable structure for tumor targeting and reduction-triggered release. Statement of Significance Hyaluronic acid (HA) can be served as micelle carriers and targeting ligands to tumor cells. However, the effects of drug conjugation densities on the physical profile and biological performance of resulting micelles have never been investigated. In the current study, camptothecin is conjugated on HA with reduction-sensitive linkers, and the substitution degrees of camptothecin on HA backbone vary from around 4–20%. The micelles with a substitution degree of around 15% achieve a better balance between the cellular uptake and reduction-triggered drug release and a higher cytotoxicity than others. It demonstrates a feasible strategy to develop drug-HA conjugate micelles with a concise and tunable structure for tumor targeting and reduction-triggered release.
研究领域:
药学
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纳米技术
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癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Dong-Yang Zhang,Hengke Liu,Muhammad Rizwan Younis,Shan Lei,Chen Yang,Jing Lin,Junle Qu,Peng Huang
Acute kidney injury (AKI) is a common kidney disease with high mortality rate, while surprisingly, the supportive treatment and renal replacement are the only available clinical treatment options to date. The onset of AKI is often triggered by excessive toxic reactive oxygen/nitrogen species (RONS), and hence, the development of antioxidants with high renal accumulation and effective renal clearance is highly demanded to consume RONS in the kidneys. In this study, we developed ultrasmall polyvinylpyrrolidone-coated platinum nanoparticles (Pt NPs-PVP, ~3 nm) as multienzyme mimetics (catalase, peroxidase, and superoxide dismutase). Thanks to their excellent RONS scavenging ability, Pt NPs-PVP effectively reduced the hydrogen peroxide induced cellular damage. Analytical (inductively coupled plasma mass spectrometry) as well as imaging (photoacoustic and computed tomography) techniques revealed the preferential renal uptake and high enrichment of ultrasmall Pt NPs-PVP after intravenous administration, offering remarkable relief of the clinical symptoms of glycerol-induced AKI mice without any apparent systemic toxicity in vivo . Importantly, because of their ultrasmall size, Pt NPs-PVP exhibited rapid excretion from healthy mice, presenting relatively low toxicity and side effects. In conclusion, our work demonstrated ultrasmall Pt nanozyme as a state of the art antioxidant for dual-modal imaging guided treatment of AKI with improved treatment efficacy.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
治疗诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Yayun Peng,Dongzhi Yang,Weifei Lu,Xiongwei Hu,Hao Hong,Ting Cai
Various carbonaceous nanomaterials , including fullerene , carbon nanotube , graphene, and carbon dots , have attracted increasing attention during past decades for their potential applications in biological imaging and therapy. In this study, we have developed a fullerene-based tumor-targeted positron emission tomography (PET) imaging probe. Water-soluble functionalized C 60 conjugates were radio-labeled with 64 Cu and modified with cyclo (Arg-Gly-Asp) peptides (cRGD) for targeting of integrin α v β 3 in glioblastoma. The specificity of fluorescein-labeled C 60 conjugates against cellular integrin α v β 3 was evaluated in U87 MG (integrin α v β 3 positive) and MCF-7 cells (integrin α v β 3 negative) by confocal fluorescence microscopy and flow cytometry. Our results indicated that cRGD-conjugated C 60 derivatives showed better cellular internalization compared with C 60 derivatives without the cRGD attachment. Moreover, an interesting finding on intra-nuclei transportation of cRGD-conjugated C 60 derivatives was observed in U87 MG cells. In vivo serial PET studies showed preferential accumulation of cRGD-conjugated C 60 derivatives at in U87 MG tumors. In addition, the pharmacokinetic profiles of these fullerene-based nanoparticles conjugated with cRGD and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) fit well with the three compartment model. The renal clearance of C 60 -based nanoparticles is remarkably fast, which makes this material very promising for safer cancer theranostic applications. Statement of significance Safety is one of the major concerns for nanomedicine and nanomaterials with fast clearance profile are highly desirable. Fullerene is a distinct type of zero-dimensional carbon nanomaterial with ultrasmall size, uniform dispersity , and versatile reactivity. Here we have developed a fullerene-based tumor-targeted positron emission tomography imaging probe using water-soluble functionalized C 60 conjugates radio-labeled with 64 Cu and modified with cyclo (Arg-Gly-Asp) peptides (cRGD) for glioblastoma targeting. The improved tumor targeting property along with fast renal clearance behavior of C 60 -based nanoparticles makes this material very promising for future safer cancer theranostic applications.
研究领域:
纳米医学
·
生物医学工程
·
分子影像
·
癌症治疗
·
放射学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 12
·3418-3429
·
IF 6.183
Yongju He,Linjie Shao,Ibrahim Usman,Yao Hu,Anqiang Pan,Shuquan Liang,Hui Xu
The balance between tumor accumulation and renal clearance has severely limited the efficacy of mesoporous silica-based drug nanocarriers in cancer therapy. Herein, a pH-responsive dissociable mesoporous silica-based nanoplatform with efficient dual-drug co-delivery, tumor accumulation and rapid clearance for cancer therapy is achieved by adjusting the wetting of the mesoporous silica surface. At pH 7.4, the synthesized spiropyran- and fluorinated silane-modified ultrasmall mesoporous silica nanoparticles (SP-FS-USMSN) self-assemble to form larger nanoclusters (denoted as SP-FS-USMSN cluster) via hydrophobic interactions, which can effectively co-deliver anticancer drugs, doxorubicin hydrochloride (Dox) and curcumin (Cur), based on the mesopores within SP-FS-USMSN and the voids among the stacked SP-FS-USMSN. At pH 4.5–5.5, the conformational conversion of spiropyran from a “closed” state to an “open” state causes the wetting of the SP-FS-USMSN surface, leading to the dissociation of the SP-FS-USMSN cluster for drug release and renal clearance. The in vitro and in vivo studies demonstrate that the Cur and Dox co-loaded SP-FS-USMSN cluster (Cur-Dox/SP-FS-USMSN cluster) possesses great combined cytotoxicity, and can accumulate into tumor tissue by its large size-favored EPR effect and potently suppress tumor growth in HepG2-xenografted mice. This research demonstrates that the SP-FS-USMSN cluster may be a promising drug delivery system for cancer therapy and lays the foundation for practical mesoporous silica-based nanomedicine designs in the future.
研究领域:
纳米技术
·
药物科学
·
癌症研究
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药物递送系统
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-23
·
IF 12.6
Yang Yang,Lv Mingzhu,Liu Ruihong,Yu Peilu,Shen Ziyi,Bai Dazhang,Zhao Peilin,Yang Jin,Tang Xiaoping,Yang Hanfeng,Yong Yuan,Jiang Guohui
Background Intracerebral haemorrhage (ICH) is a devastating neurological disorder with high morbidity and mortality rates, largely owing to the lack of effective therapeutic strategies. Growing evidence has underscored the pivotal role of ferroptosis in intracerebral haemorrhage, and its contribution to neuronal death and exacerbation of brain injury, thus establishing it as a crucial target for therapeutic intervention. In recent years, polyoxometalate nanoclusters (NCs) have been applied in various neurodegenerative diseases, demonstrating neuroprotective effects. However, their impact on brain iron content and neurological function following ICH has yet to be reported. Here, we explored the potential of tungsten-based polyoxometalate (W-POM) NCs as ferroptosis inhibitors targeting the iron metabolic pathway mediated by S100A8/A9 for the treatment of ICH. Results We successfully synthesized ultra-small reduced W-POM NCs that can rapidly cross the blood-brain barrier and are cleared through the kidney. In vitro experiments demonstrated that W-POM NCs exhibit significant and stable ROS scavenging activity while effectively alleviating iron overload and associated neuronal damage. In vivo, W-POM NCs treatment restored iron metabolism homeostasis, suppressed neuroinflammation and oxidative stress, ultimately alleviating severe neurological damage and motor deficits in ICH mice. Proteomic combined with bioinformatic analyses identified two core genes, S100A8 and S100A9, most associated with W-POM NCs intervention in ICH. Further experiments confirmed that W-POM NCs act by modulating the toll-like receptor 4/hepcidin/ferroportin signaling pathway, thereby regulating iron metabolism and reducing secondary brain injury. Conclusions This study pioneers the application of polyoxometalates in intracerebral haemorrhage, offering a novel and promising therapeutic approach for the management of ferroptosis-related brain injuries.
研究领域:
神经病学
·
药理学
·
纳米技术
·
生物化学
✓ 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）