ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Wenhai Lin,Wei Zhang,Tingting Sun,Shi Liu,Yu Zhu,Zhigang Xie
Polymeric nanoparticles (NPs) play a key role in nanoscale formulations for bioimaging, cancer treatment, and theranostics. In this work, we designed and synthesized a series of hydrophobic polymers (P1–6) with different pendent groups via one-step multicomponent Passerini reaction. These polymers possessed similar molecular structures and various biomedical functions. Interestingly, they could self-assemble into stable NPs in aqueous media. All formed NPs were redox sensitive because of the existence of disulfide bonds in the backbone. The stability of NPs in aqueous media with or without glutathione was systematically evaluated and compared. The optical performance, including fluorescence resonance energy transfer, was characterized under different conditions for those polymers with fluorescent components. Importantly, all formed NPs showed good cytocompatibility toward HeLa cells and different biological functions, including drug loading and delivery, bioimaging with variable fluorescence, and photodynamic activity, as evidenced by experiments in vitro and in vivo. These results demonstrate the great potential of multicomponent reaction to customize versatile polymeric nanoparticles for biomedical applications.
研究领域:
纳米技术
·
生物医学工程
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Bo Tian,Qiuhong Wang,Qianqian Su,Wei Feng,Fuyou Li
Triplet-triplet annihilation (TTA)-based upconversion nanocapsules (UCNCs) have great potential in biological and medical applications. However, there are numerous unresolved issues with respect to the safety of these novel nanomaterials . In this work, for the first time, we studied the in vivo biodistribution of UCNCs which were synthesized by co-loading platinum (II)-tetraphenyl-tetrabenzoporphyrin (PtTPBP) and boron dipyrromethene derivative (BDP) into bovine serum albumin (BSA)-stabilized soybean oil droplets , and systematically assessed the potential toxicity of UCNCs both in vitro and in vivo . The results showed that UCNCs had no significant influence on the proliferation or the migration of HeLa cells even when the dosage was increased to 12 mg/mL. The biodistribution results demonstrated that UCNCs mainly accumulated in the mononuclear phagocyte system (MPS) including the liver and spleen after intravenous injection of the nanocapsules. When mice were intravenously injected with 1200 mg/kg of the UCNCs over a period of 60 days, no noticeable toxicity was observed under these treatment conditions as shown by body weight results, histological analyses, hematological analyses and blood biochemical examinations. This research inspires further studies on UCNCs for biomedical applications .
研究领域:
纳米技术
·
生物医学工程
·
毒理学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2013
·
IF 0
Li Lv,Yuanyuan Shen,Min Li,Xiaofen Xu,Mingna Li,Shengrong Guo,Shengtang Huang
A novel 4-arm poly(ethylene glycol)-block-poly(anhydride-esters) amphiphilic copolymer (4-arm PEG-b-PAE) was synthesized by esterization of 4-arm poly(ethylene glycol) and poly(anhydride-esters) which was obtained by melt polycondensation of α-, ω-acetic anhydride terminated poly(L-lactic acid). The obtained 4-arm PEG-b-PAE was characterized by 1H-NMR and gel permeation chromatography. The critical micelle concentration of 4-arm PEG-b-PAE was 2.38 μg/mL. The curcumin-loaded 4-arm PEG-b-PAE micelles were prepared by a solid dispersion method and the drug loading content and encapsulation efficiency of the micelles were 7.0% and 85.2%, respectively. The curcumin-loaded micelles were spherical with a hydrodynamic diameter of 151.9 nm. Curcumin was encapsulated within 4-arm PEG-b-PAE micelles amorphously and released from the micelles, faster in pH 5.0 than pH 7.4, presenting one biphasic drug release pattern with rapid release at the initial stage and slow release later. The hemolysis rate of the curcumin-loaded 4-arm PEG-b-PAE micelles was 3.18%, which was below 5%. The IC50 value of the curcumin-loaded micelles against Hela cells was 10.21 μg/mL, lower than the one of free curcumin (25.90 μg/mL). The cellular uptake of the curcumin-loaded micelles in Hela cell increased in a time-dependent manner. The curcumin-loaded micelles could induce G2/M phase cell cycle arrest and apoptosis of Hela cells.
研究领域:
药学
·
材料科学
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纳米技术
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
ACS Nano
·
2024
·
IF 15.8
Jianshuai Bao,Jiefei Wang,Sudi Chen,Shiqi Liu,Zhen Wang,Weiwei Zhang,Chenhui Zhao,Yuling Sha,Xiaoyan Yang,Yusen Li,Yong Zhong,Feng Bai
Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal–organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu2+) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu2+ was reduced to Cu+ by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H2O2) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI) results verified this nanotheranostic could target the HeLa tumor to greatly promote the self-enhanced effect of chemotherapy/cuproptosis and tumor inhibition efficiency. The work helped to elucidate the controlled assembly of multiresponsive nanotheranostics and the high-specificity ROS regulation for application in anticancer therapy.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
·
化学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Ke Wang,Sicheng Zhai,Yuanyuan Qin,Mengke Hao,Siqi Su,Shuming Li,Xuexue Tang
Controlled drug release with on demand holds great promise for cancer therapy. Light-degradable nanocarriers have gained increasing attention for designing controllable drug delivery systems due to their spatiotemporally controllable properties. Herein, a high luminescent and light-degradable nanocarrier is constructed by intercalating glutathione-capped gold nanoclusters (AuNCs) into zeolitic imidazolate framework-8 (ZIF-8) via competitive coordination assembly, named as AuNC@ZIF-8, for light-triggered drug release. Glutathione-capped AuNCs and 2-methylimidazole (MIm) competitively coordinated with Zn2+ to form AuNC@ZIF-8 via one step process in aqueous solution. Specifically, the obtained AuNC@ZIF-8 has a high quantum yield of 52.96 % and displays a distinctive property of photolysis. The competitive coordination interactions within AuNC@ZIF-8 were evidenced by X-ray diffraction and X-ray photoelectron spectroscopy, in which Zn2+ strongly coordinated with the N of MIm and weakly coordinated with the carboxyl/amino groups in glutathione of AuNCs. Under light irradiation, the Au-S bond on AuNCs breaks, enhancing the coordination ability between carboxyl/amino groups and Zn2+ enhance. This leads to the collapse of the crystal structure of AuNC@ZIF-8 and subsequent fluorescence quenching. Additionally, AuNC@ZIF-8 is successfully employed as luminescent nanocarriers of anticancer drugs to form drug-AuNC@ZIF-8, in which three typical anticancer drugs are selected due to different coordination interaction. The obtained smart drug-AuNC@ZIF-8 can be effectively internalized into HeLa cells and degraded in response to blue light, with negligible dark cytotoxicity and high light cytotoxicity. This study highlights the crucial role of competitive coordination interactions in synthesizing functional materials with fluorescence efficiency and photolytic properties.
研究领域:
纳米技术
·
材料科学
·
癌症研究
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药学
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光化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2013
·
IF 5.008
Tianbin Ren,Wei Wu,Menghong Jia,Haiqing Dong,Yongyong Li,Zhouluo Ou
In the treatment of cancer, multidrug resistance (MDR) has been the major obstacle to the success of chemotherapy. The underlying mechanism relies on the overexpression of drug-efflux transporters that prevent the intracellular transport of the drug. In this study, reduction-cleavable vesicles were designed and developed with efficient glutathione-mediated drug-release behavior for reversing drug resistance. Polymeric vesicles were self-assembled from triblock copolymers with disulfide-bond-linked poly(ethylene glycol) (PEG) and poly(ε-benzyloxycarbonyl-l-lysine) (PzLL). Observations from transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) outline an obvious hollow structure surrounded by a thin outer layer, indicating the successful formation of the vesicles. Using fluorescently detectable doxorubicin hydrochloride (DOX·HCl) as the model drug, a significant acceleration of drug release regulated by glutathione (GSH) was found (>3-fold difference). Upon incubation of the DOX·HCl-loaded polymeric vesicles with the HeLa cervical cancer cell line exposed to glutathione, an enhanced nuclear accumulation of DOX·HCl was observed, elicited by the preferred disassembly of the vesicle structure under reducing conditions. Importantly, by using the gemcitabine hydrochloride (GC·HCl)-resistant breast cancer cell line MDA-MB-231, it was found that cell viability was significantly reduced after treatment with GC·HCl-loaded polymeric vesicles, indicating that these vesicles can help to reverse the drug resistance.
研究领域:
药理学
·
癌症研究
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聚合物化学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Yijia Yu,Wenjuan Xia,Wenjin Wang,Zhaoqiang Wu,Hong Chen
Hydrophilic antifouling polymers provide excellent antifouling effects under usual short-term use conditions, but the long-term accumulation of contaminants causes them to lose their antifouling properties. To overcome this drawback, surface-initiated ring-opening graft polymerization (SI-ROP) was performed on the surface of the material by applying the cyclic carbide monomer 4′-(fluorosulfonyl)benzyl-5-methyl-2-oxo-1,3-dioxane-5-carboxylate (FMC), which contains a sulfonylfluoride group on the side chain, followed by a “sulfur(IV)-fluorine exchange” (SuFEx) post click modification reaction to link the hydrophilic polyethylene glycol (PEG) to the polyFMC (PFMC) brush, and a novel antifouling strategy for self-polishing dynamic antifouling surfaces was developed. The experimental results showed that the antifouling surface could effectively prevent the adsorption of proteins such as bovine serum albumin (BSA, ∼96.4%), fibrinogen (Fg, ∼87.8%) and lysozyme (Lyz ∼69.4%) as well as the adhesion of microorganisms such as the bacteria Staphylococcus aureus ( S. aureus ) (∼87.5%) and HeLa cells (∼67.2%). Moreover, the enzymatically self-polished surface still has excellent antifouling properties. Therefore, this modification method has potential applications in the field of biosensors and novel antifouling materials.
研究领域:
材料科学
·
表面化学
·
生物医学工程
·
高分子科学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Jingyuan Ji,Chenjia Zhao,Chen Hua,Lu Lu,Yuan Pang,Wei Sun
As attempting personalized medicine, 3D-printed tissue engineering scaffolds are employed to combine with therapeutic proteins/peptides especially in the clinical treatment of infectious diseases, genetic diseases, and cancers. However, current drug-loading methods, such as immersion and encapsulation, usually lead to the burst release of the drugs. To address these issues, we proposed an integrated strategy toward the long-term controlled release of protein. In this study, patient-customized 3D scaffolds incorporated with drug-loaded microspheres were printed to realize the effective delivery of the anti-human papillomavirus (anti-HPV) protein after cervical conization in the treatment of cervical cancer. The 3D-printed scaffold could provide mechanical support to the defect site and ensure local release of the drug to avoid systemic administration. Meanwhile, microspheres serve as functional components to prevent the inactivation of proteins, as well as regulate their release period to meet the time requirement of different treatment courses. The research also utilized bovine serum albumin as a model protein to validate the feasibility of these scaffolds as a generic technology platform. The bioactivity of the released anti-HPV protein was validated using a pseudovirus model, which demonstrated that the microsphere encapsulation would not cause protein denaturation during the scaffold fabrication process. Besides, 3D-printed scaffolds incorporated with carboxylated chitosan microspheres were biocompatible and beneficial for cell attachment, which have been demonstrated by favorable cell viability and better coverage results for HeLa and HFF-1. This study highlights the great potential of scaffolds incorporated with microspheres to serve as tissue engineering candidate products with the function of effective protein delivery in a long-term controlled manner and personalized shapes for clinical trials.
研究领域:
生物医学工程
·
药学
·
组织工程
·
癌症研究
·
药物递送系统
·
个性化医疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Zhiyuan Li,Liu Zhang,Quanshun Li
Herein, N -acetyl- l -leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine 2000 . Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential as biocompatible carriers for realizing effective tumor gene therapy.
研究领域:
癌症生物学
·
分子生物学
·
基因治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2017
·
IF 2.714
Tong-Xian Zhang,Chen Zhan,Yu Chen,Li-Ping Yu
Hyperbranched polymers were successfully used as reductant and stabilizer for the synthesis of stable water-soluble fluorescent gold nanoclusters (AuNCs) through a one-step bottom-up strategy. The hyperbranched polymers having such performance were acetamide terminated hyperbranched poly(amidoamines) (HPA-Acs) with disulfide functional groups. Small sized (less than 2 nm) AuNCs were formed under the optimal conditions of 80 °C, weak acidic condition (around pH 4.3) for 15–20 h. Through adjusting the feed ratio of HAuCl 4 to HPA-Ac, the emitting light could be tuned from yellow to near-infrared. The measurements of UV–vis spectroscopy, transmission electron microscopy and X-ray photoelectron spectroscopy further verified the formation of AuNCs. The quantum yields of the yellow and near-infrared fluorescent AuNCs were ca. 3.6% and 1.2%, respectively. The as-prepared AuNCs showed an excellent stability in a wide pH range (pH 2–12) and possessed low cytotoxicity for cancer HeLa cell, making it a suitable candidate for bioimaging.
研究领域:
纳米技术
·
材料科学
·
化学
·
生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Ping Sun,Na Xu,Xue Zhang,Yun-Fei Gao,Jia-Yin Zhang,Qi-Ming Zhang,Chen Liang,Ri-Lei Yu,Ya-Mu Xia,Wei-Wei Gao
In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[ de ]isoquinoline-1,3(2H)-dione ( D-11 ) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[ de ]isoquinoline-1,3(2H)-dione ( D-12 ) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 ( D-12 ) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ct DNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12 , the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 ( D-12 ) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV–vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 ( D-12 ) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.
研究领域:
药物化学
·
生物化学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2016
·Vol. 40
·期 10
·8397-8407
·
IF 3.277
Beibei Lu,Lei Li,Jianning Wu,Lulu Wei,Jun Hou,Zhiyong Liu,Xuhong Guo
Well-defined dual pH and temperature responsive triblock star-shaped amphiphilic copolymers of β-cyclodextrin-g-poly(2-hydroxyethylmethacrylate)-b-poly(N-isopropylacrylamide)-b-poly(2-(dimethylamino)ethylmethacrylate) (β-CD-g-(PHEMA-b-PNIPAM-b-PDMAEMA)) were synthesized by the combination of reversible addition–fragmentation chain transfer (RAFT) polymerizations. The chemical structures and compositions of these copolymers were characterized by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), and gel permeation chromatography (GPC) measurements. Subsequently, the obtained triblock copolymers could self-assemble into micelles in aqueous solution owing to their amphiphilic property resulting from the hydrophobic β-CD core and the hydrophilic PHEMA, PNIPAM, and PDMAEMA segments, which were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The triblock copolymer nanoparticles exhibited two separate lower critical solution temperatures (LCSTs) and these triblock copolymers in aqueous solutions were investigated at the different pH values of 5.0 and 7.4 as doxorubicin (DOX) delivery systems for controlled release. Polymeric micelles exhibited a pH controlled release performance. Investigation of DOX release from the micelles indicated that the release rate of the drug could be effectively controlled by altering the pH, encapsulating DOX in neutral surroundings (blood circulation or extracellular matrix) and triggering DOX release in acidic surroundings (intracellular endosomes). CCK-8 assays and confocal laser scanning microscopy (CLSM) against HeLa cells indicated that the polymeric micelles themselves had no associated cytotoxicity and possessed good biodegradability and biocompatibility and that the micelles identified the location of the DOX in the HeLa cells. On the other hand, the DOX-loaded micelles possessed a high cytotoxicity to HeLa cells and exhibited inhibition of the proliferation of HeLa cells. Hence, this type of biodegradable, biocompatible, and stimuli-responsive copolymer could serve as a promising material for drug delivery.
研究领域:
高分子化学
·
材料科学
·
药学
·
生物医学工程
✓ 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）