Nanoscale
·
2014
·Vol. 6
·期 21
·12580-12590
·
IF 6.739
Haiyan Chen,Bowen Li,Min Zhang,Kang Sun,Yiran Wang,Kerui Peng,Mengdi Ao,Yiran Guo,Yueqing Gu
Nanomedicine platforms that have the potential to simultaneously provide the function of molecular imaging and therapeutic treatment in one system are beneficial to address the challenges of cancer heterogeneity and adaptive resistance. In this study, Cyclic RGD peptide (cRGD), a less-expensive active tumor targeting tri-peptide, and doxorubicin (DOX), a widely used chemotherapeutic drug, were covalently attached to Ag2S quantum dots (QDs) to form the nano-conjugates Ag2S-DOX-cRGD. The optical characterization of Ag2S-DOX-cRGD manifested the maintenance of QDs fluorescence, which suggested the potential of Ag2S for monitoring intracellular and systemic drug distribution. The low biotoxicity of Ag2S QDs indicated that they are promisingly safe nanoparticles for bio-applications. Furthermore, the selective imaging and favorable tumor inhibition of the nanoconjugates were demonstrated at both cell and animal levels. These results indicated a promising future for the utilization of Ag2S QDs as a kind of multi-functional nano platform to achieve imaging-visible nano-therapeutics.
研究领域:
纳米医学
·
肿瘤学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 7
·期 1
·92-103
·
IF 5.831
Huixiang Yan,Jingqin Chen,Ying Li,Yuanyuan Bai,Yunzhu Wu,Zonghai Sheng,Liang Song,Chengbo Liu,Hai Zhang
Although photoacoustic imaging combined with second near infrared (NIR II) molecular probes for tumor diagnosis has drawn tremendous attention during the past few decades, the targeted photoacoustic imaging of orthotopic hepatocellular carcinoma (HCC) still remains a challenge due to high liver vascularization and non-specificity of probes in liver tumors. Herein, we report on cyclic arginine–glycine–aspartic acid (cRGD) peptide conjugated ultrasmall CuS nanoparticles (CuS@BSA-RGD NPs) which encapsulate bovine serum albumin (BSA) and possess high optical absorption at 1064 nm. The encapsulation of BSA results in great biocompatibility of CuS@BSA-RGD NPs along with excellent photostability and physiological stability. The cRGD conjugation enables the improvement of tumor uptake of CuS@BSA-RGD NPs by virtue of its positive tumor cell targeting capability. The efficient accumulation of CuS@BSA-RGD NPs in the tumor over time after intravenous administration to orthotopic HCC bearing mice was achieved, which resulted in highly sensitive photoacoustic visualization of the tumor region. Toxicity studies indicate that CuS@BSA-RGD NPs exhibited negligible systemic toxicity in vivo. The results demonstrate that the CuS@BSA-RGD NPs might hold great promise for future imaging and diagnosis of cancer.
研究领域:
生物医学工程
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肿瘤学
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分子影像学
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产品关联
DOI
PubMed
高影响因子
POLYMER BULLETIN
·
2022
·Vol. 79
·期 12
·10555-10571
·
IF 2.843
Yu Lili,Yao Lin,Yang Kuan,Fei Wenling,Chen Qingqing,Qin Lan,Liu Shaojing,Cao Min,Liu Qian,Qin Bei
Nano core–shell drug carriers with high stability, low toxicity, and targeted drug delivery are significance for the delivery of anti-tumor drugs. In this study, Albumin from bovine serum (BSA), serving as a capping agent, was conjugated to MSNs via a cleavable disulfide bond to generate a redox-responsive nanocarrier (MSNs@BSA). Subsequently, cRGD peptide, as a targeting ligand, was modified on the particle surface by a protein cross-linker to obtain nanoparticles with tumor cell-targeting properties (RGD-MSNs@BSA). The construction of RGD-MSNs@BSA was confirmed by DLS analysis, scanning electron microscope (SEM), transmission electron microscopy (TEM), electron dispersive spectroscopy (EDS), X-Ray Diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR), respectively. It was displayed that the model anticancer drug doxorubicin (DOX) was efficiently and stably encapsulated in RGD-MSNs@BSA in the absence of glutathione (GSH), and an outbreak of DOX was observed when the particles were exposed to a GSH-containing environment. It demonstrated that disulfide-linked BSA capping can increase the drug loading stability, while enduing it redox sensitivity. Flow cytometry and fluorescence microscope tests displayed that cellular uptake of RGD-MSNs@BSA was much higher than that of particles without cRGD and free DOX. These results indicated that RGD-MSNs@BSA can increase drug tumor-targeting and drug cellular uptake.
研究领域:
纳米医学
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药理学
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生物材料科学
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产品关联
DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Mingyu You,Lei Zhang,Tobias A. Gmür,Kaihuan Zhang,Stefan Zürcher,Wen Li,Guangyin Yuan,Nicholas D. Spencer,Jia Pei
Synthetic pure hydroxyapatite (HA), though widely investigated as an artificial orthopedic implant material, has neither anti-infection properties nor innate interfacial bioactivity. Ideally, surface modification of this material needs to be developed with simultaneous anti-microbial capacity and superior cytocompatibility. Herein, graft copolymers of a PAA backbone functionalized with a high density of polyethylene glycol (PEG), and varying grafting densities of cyclic Arg-Gly-Asp-d-Phe-Cys peptides (cRGD) end-grafted onto the PEG chains have been designed and synthesized. Systematic study on the grafted anchoring groups first indicates a synergistic binding mechanism of the copolymer to HA surface, involving electrostatic interaction of the protonated amino (–NH 3 + ) with negatively charged HA, assisted with coordination bonding through the nitrodopamine (ND) group. The PEGylated graft copolymers are demonstrated to firmly adsorb to the HA surface as an ultrathin self-assembly layer from a HEPES buffer solution, showing stability with insignificant desorption and effective inhibition of non-specific protein adsorption evaluated by XPS and QCM-D assays. Direct adhesion assays confirm that HA, modified with the density-optimized cRGD/PEG-functionalized graft polymer, can considerably promote osteoblast attachment, while preventing different strains of bacteria adhesion in the initial phase.
研究领域:
材料科学
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生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2019
·
IF 3.131
Lu Tian,Lei Tao,Hongyan Li,Shili Zhao,Yunfang Zhang,Shen Yang,Jianfeng Xue,Xianfeng Zhang
The exploration of drug delivery systems based on mesoporous structure materials shows great promise in nanomedcine. Herein, a multifunctional nanoplatform based on cyclic arginine-glycine-aspartic acid (cRGD) peptide-conjugated hollow mesoporous carbon nanoparticles (cRGD-HMCN) was developed to realize near-infrared (NIR)/pH-responsive drug release and targeted chemo-photothermal therapy. The cRGD-HMCN exhibited a high doxorubicin (DOX) loading efficiency of 246 μg/mg cRGD-HMCN and pH/NIR-responsive controlled drug release behavior. Also, taking the advantage of the high photothermal conversion efficiency, the HMCN could serve as a photothermal agent to realize photothermal therapy. The in vitro experimental results confirmed that DOX-loaded cRGD-HMCN (cRGD-HMCN@DOX) can significantly improve the therapeutic efficacy toward PC3 cells upon NIR laser irradiation, which was significantly more potent than that for non-targeted HMCN@DOX. More importantly, in vivo data from in the prostatic carcinoma (PC3) xenograft mouse model show that the tumor growth is effectively inhibited by treatment with cRGD-HMCN@DOX plus NIR irradiation with fewer side effects. Importantly, the synergistic group showed superior tumor growth inhibition as compared to that of nontargeted group and any monotherapy. Thus, it is expected that the HMCN could be a potential nanosystem to realizesynergistic chemo-photothermal therapy for cancer treatment.
研究领域:
纳米医学
·
肿瘤学
·
药物递送系统
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产品关联
DOI
高影响因子
Biomolecules
·
2022
·Vol. 12
·期 9
·1277
·
IF 6.064
Mengjun Wang,Hongliang He,Di Liu,Ming Ma,Yu Zhang
Although cerium oxide nanoparticles are attracting much attention in the biomedical field due to their unique physicochemical and biological functions, the cerium oxide nanoparticles greatly suffer from several unmet physicochemical challenges, including loss of enzymatic activity during the storage, non-specific cellular uptake, off-target toxicities, etc. Herein, in order to improve the targeting property of cerium oxide nanoparticles, we first modified cerium oxide nanoparticles (CeO2) with polyacrylic acid (PAA) and then conjugated with an endothelium-targeting peptide glycine-arginine-aspartic acid (cRGD) to construct CeO2@[email protected]The physiochemical characterization results showed that the surface modifications did not impact the intrinsic enzymatic properties of CeO2, including catalase-like (CAT) and superoxide dismutase-like (SOD) activities. Moreover, the cellular assay data showed that CeO2@[email protected]exhibited a good biocompatibility and a higher cellular uptake due to the presence of RGD targeting peptide on its surface. CeO2@[email protected]effectively scavenged reactive oxygen species (ROS) to protect cells from oxidative-stress-induced damage. Additionally, it was found that the CeO2@[email protected]converted the phenotype of macrophages from proinflammatory (M1) to anti-inflammatory (M2) phenotype, inhibiting the occurrence of inflammation. Furthermore, the CeO2@[email protected]also promoted endothelial cell-mediated migration and angiogenesis. Collectively, our results successfully demonstrate the promising application of CeO2@[email protected]in the future biomedical field.Keywords:cerium oxide nanoparticles;CeO2@PAA;CeO2@[email protected];antioxidant;anti-inflammatory;angiogenesis
研究领域:
纳米技术
·
生物医学工程
·
药学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 11
·1932-1940
·
IF 4.872
Jing-Jing Hu,Li-Han Liu,Ze-Yong Li,Ren-Xi Zhuo,Xian-Zheng Zhang
In this paper, we report on an intelligent mesoporous silica-based multifunctional theranostic nanoplatform (designated as MMTNP) for tumor imaging as well as controlled drug release. This theranostic nanoplatform consists of MCM-41 typical mesoporous silica nanoparticles (MSNs) as a hydrophobic drug carrier, matrix metalloprotease-2 (MMP-2) activated fluorescence imaging peptides on the surface of MSNs served as diagnostic probes as well as enzyme-responsive nanovalves blocking the pores, and cRGD peptides further functionalized on the surface of MSNs for tumor targeting. In the absence of MMP-2 conditions, the proximity between the fluorescent dye 5(6)-carboxytetramethylrhodamine hydrochloride (TAMRA) and the quencher 4,4-dimethylamino-azobenzene-4′-carboxylic acid (Dabcyl) on the surface of MSNs resulted in no fluorescence. When the drug loaded nanoplatform arrived at tumor tissue with overexpressed MMP-2, the fluorescence of TAMRA became recovered efficiently due to the hydrolysis of the MMP-2 sensitive peptide substrate, realizing tumor imaging and triggering drug release. In addition, the further introduced cRGD peptide significantly enhanced the targeting efficiency through receptor-mediated endocytosis in tumor cells.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Jianbin Mo,Lizhen He,Bin Ma,Tianfeng Chen
The blood–brain barrier (BBB) is the main bottleneck to prevent some macromolecular substance entering the cerebral circulation, resulting the failure of chemotherapy in the treatment of glioma. Cancer nanotechnology displays potent applications in glioma therapy owing to their penetration across BBB and accumulation into the tumor core. In this study, we have tailored the particle size of mesoporous silica nanoparticles (MSNs) through controlling the hydrolysis rate and polycondensation degree of reactants, and optimized the nanosystem that could effectively penetrate BBB and target the tumor tissue to achieve enhanced antiglioma efficacy. The nanoparticle was conjugated with cRGD peptide to enhance its cancer targeting effect, and then used to load antineoplastic doxorubicin. Therefore, the functionalized nanosystem (DOX@MSNs) selectively recognizes and binds to the U87 cells with higher expression level of ανβ3 integrin, sequentially enhancing the cellular uptake and inhibition to giloma cells, especially the particle size at 40 nm. This particle could rapidly enter cancer cells and was difficult to excrete outside the cells, thus leading to high drug accumulation. Furthermore, DOX@MSNs exhibited much higher selectivity and anticancer activity than free DOX and induced the glioma cells apoptosis through triggering ROS overproduction. Interestingly, DOX@MSNs at about 40 nm exhibited stronger permeability across the BBB, and could disrupt the VM-capability of glioma cells by regulating the expression of E-cadherin, FAK, and MMP-2, thus achieving satisfactory antiglioblastoma efficacy and avoiding the unwanted toxic side effects to normal brain tissue. Taken together, these results suggest that tailoring the particle size of MSNs nanosystem could be an effective strategy to antagonize glioblastoma and overcome BBB.
研究领域:
纳米医学
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Jingxin Mo,Xianjue Chen,Meiying Li,Wenxu Liu,Wei Zhao,Lee Yong Lim,Richard D. Tilley,J. Justin Gooding,Qinghua Li
Glioblastoma is hard to be eradicated partly because of the obstructive blood–brain barrier (BBB) and the dynamic autophagy activities of glioblastoma. Here, hydroxychloroquine (HDX)-loaded yolk–shell upconversion nanoparticle (UCNP)@Zn0.5Cd0.5S nanoparticle coating with the cyclic Arg-Gly-Asp (cRGD)-grafted glioblastoma cell membrane for near-infrared (NIR)-triggered treatment of glioblastoma is prepared for the first time. UCNPs@Zn0.5Cd0.5S (abbreviated as YSN, yolk–shell nanoparticle) under NIR radiation will generate reactive oxygen species for imposing cytotoxicity. HDX, the only available autophagy inhibitor in clinical studies, can enhance cytotoxicity by preventing damaged organelles from being recycled. The cRGD-decorated cell membrane allowed the HDX-loaded nanoparticles to efficiently bypass the BBB and specifically target glioblastoma cells. Exceptional treatment efficacy of the NIR-triggered chemotherapy and photodynamic therapy was achieved in U87 cells and in the mouse glioblastoma model as well. Our results provided proof-of-concept evidence that HDX@YSN@CCM@cRGD could overcome the delivery barriers and achieve targeted treatment of glioblastoma.
研究领域:
纳米医学
·
癌症研究
·
神经科学
·
药剂学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Mengmeng Dong,Yumeng Liu,Yuting Xiao,Qingqing Wu,Mingjing Guan,Zunqiang Xiao,Junwei Liu,Lidong Cao,Yi Lu
Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive forms of liver cancer, with limited therapeutic options and a high recurrence rate. Traditional treatments include surgery and systemic therapy, but systemic therapy has side effects, such as poor specificity, systemic toxicity, and drug resistance. Herein, we designed a multimodal diagnostic and therapeutic-integrated nanosphere for packaging and delivering lenvatinib (LVN). The system was constructed using a PLGA-PEG polymer and modified by cyclic peptide cRGD with high selectivity and affinity for cancer cell integrins. Next, the system was loaded with lenvatinib (LVN) and IR780 photosensitizer, providing a satisfactory basis for photodynamic therapy/photothermal therapy (PDT/PTT) treatment. The nanoparticles could actively and passively target HCC cells and hydrolyze them in an acidic environment to release photosensitizers and LVN, which played significant roles in diminishing tumor cells. After 808 nm laser irradiation, the PDT and PTT effects induced by IR780 synergistically increased the function of LVN by inducing ferroptosis and apoptosis. In addition, in vivo and in vitro experiments showed that PPR@LVN/IR780 nanoparticles could inhibit the growth of tumors under 808 nm laser irradiation without obvious damage to other organs. At the same time, we also used high-throughput sequencing technology to further explore the underlying mechanisms of the nanoparticles. This work not only provided a liver-targeted drug delivery strategy based on first-line systemic therapy drugs but also provided an efficient and synergistic visualization imaging method for fluorescence imaging (FLI), photoacoustic imaging (PAI), and photothermal imaging (PTI) to realize integrated multimodal diagnosis and treatment.
研究领域:
纳米医学
·
肿瘤学
·
药物递送系统
·
光动力疗法
·
光热疗法
·
分子成像
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Zhenyu Chen,Zhongbing Liu,Shuzao Wang,Cai Cheng,Xiaoduan Sun,Zerong Liu,Jun Wei,Jun Jiang,Huaqi Lan,Meiling Zhou,Pei Jing,Yan Lin,Xiangyu Zhou,Zhirong Zhong
Background Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug with good analgesic and anti-inflammatory effects. However, it suffers from poor solubility, short circulation time, and off-target binding profile, which significantly limit its clinical application. Here, we loaded FA into stealth lipid microspheres modified with the arginine-glycine-aspartic acid (RGD) peptide (cRGD-FA-SLM), and examined the therapeutic potential of the resulting platform for the treatment of rheumatoid arthritis (RA).Methods cRGD-FA-SLM was prepared by high pressure homogenization, and its toxicity and uptake by macrophages were examined using cultures of RAW264.7 cells. Hemolysis and hepatotoxicity tests were performed to assess the safety of the developed platform, while its pharmacokinetics, biodistribution, and therapeutic efficacy were investigated in a collagen-induced arthritis rat model.Results cRGD-FA-SLM showed homogeneous spherical morphology and efficient encapsulation of FA. The developed platform was non-toxic to normal macrophages and was selectively internalized by lipopolysaccharide-activated macrophages in vitro, while it distributed mainly to arthritic joints and significantly prolonged FA in circulation in vivo. cRGD-FA-SLM also significantly reduced the expression of prostaglandin E2 and alleviated joint edema and bone erosion, showing prolonged analgesic effects in arthritic rats.Conclusion cRGD-FA-SLM shows good inflammation-targeting ability and prolongs drug circulation in vivo, suggesting promise as an anti-inflammatory and analgesic agent for targeted RA treatment.
研究领域:
药学
·
纳米技术
·
免疫学
·
药理学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Zhechang Chen,Caijie Yuan,Yaxin Ye,Bitao Lu,Enling Hu,Fei Lu,Kun Yu,Ruiqi Xie,Guangqian Lan
Arterial thrombosis is a critical thrombotic disease that poses a significant threat to human health. However, the existing clinical treatment of arterial thrombosis lacks effective targeting and precise drug release capability. In this study, we developed a system for targeted delivery and on-demand release in arterial thrombosis treatment. The carrier was constructed using chitosan (CS) and fucoidan (Fu) through layer-by-layer assembly, with subsequent surface modification using cRGD peptide. Upon encapsulation of urokinase-type plasminogen activator (uPA), the resulting therapeutic drug delivery system, uPA-CS/Fu@cRGD, demonstrated dual-targeting abilities towards P-selectin and αIIbβ3, as well as pH and platelet-responsive release properties. Importantly, we have demonstrated that the dual targeting effect exhibits higher targeting efficiency at shear rates simulating thrombosed arterial conditions (1800 s −1 ) compared to single targeting for the first time. In the mouse common iliac artery model, uPA-CS/Fu@cRGD exhibited great thrombolytic capability while promoting the down-regulation of coagulation factors (FXa and PAI-1) and inflammatory factors (TNF-α and IL-6), thus improving the thrombus microenvironment and exerting potential in preventing re-occlusion. Our dual-target and dual-responsive, fucoidan-based macrovesicle represent a promising platform for advanced drug target delivery applications, with potential to prevent coagulation tendencies as well as improving thrombolytic and reducing the risk of re-occlusion.
研究领域:
药学
·
生物医学工程
·
血栓研究
·
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）