Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 23
·4110-4118
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IF 4.872
Jing Zhang,Guangyu Hao,Chenfei Yao,Su Hu,Chunhong Hu,Bingbo Zhang
Glioma stem cells (GSCs) are considered the key to the occurrence, development, invasion, recurrence and sensitivity to treatment of brain tumors. Precise molecular imaging of GSCs by means of probes in vivo has therefore become a premise of solving the above problems. Herein, a sensitive, specific, accurate and biocompatible molecular nanoprobe is reported with MR/fluorescence imaging modalities for CD133+ glioma tumor bimodal targeted imaging. Cd-free high quality CuInS2/ZnS core/shell quantum dots (QDs) were synthesized for fluorescence imaging; DTPA-coupled BSA with Gd3+ chelation (BSA-DTPAGd) were prepared and used both for phase transfer of hydrophobic CuInS2/ZnS QDs and MR imaging modality. The resulting hydrophilic paramagnetic QDs (pQDs) were then linked with anti-CD133 monoclonal antibody, pQDs-CD133mAb denoting the framework of the entire molecular probe, for tumor targeting. The obtained pQDs-CD133mAb has a proper size (ca. 45 nm) and good colloidal stability. It exhibits a high quality fluorescent emission (ca. 630 nm) together with high longitudinal relaxivity (r1 = 15.2 mM−1 s−1) compared with that of commercial Magnevist (r1 = 3.12 mM−1 s−1). Dual modal imaging in vitro and in vivo shows potent tumor enhancement with administration of pQDs-CD133mAb. A biodistribution study indicates hepatobiliary and renal processing of pQDs-CD133mAb with no obvious toxicity. It could be therefore concluded, with a dual-modal imaging and targeting strategy, pQDs-CD133mAb presents a great potential as an alternative for accurate diagnosis of glioma.
研究领域:
医学影像学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2024
·
IF 4
Yang Tao,Maoxin Du,Meihua Zhu,Yinyue Wang,Yusong Fei,Yu-Qiang Zhao,Junjie Ma,Ruifeng Fan,Fang Dai,Jingchao Chen,Junlin Yin,Baomin Fan,Guangzhi Zeng
The peptide–drug conjugate (PDC) has emerged as one of the new approaches for cancer therapy, which has the advantages of improved drug target ability and reduced adverse effects compared with the traditional chemotherapy. CD133 is a surface antigen specific to cancer stem cells, which are thought to be responsible for the self-renewal, proliferation, metastasis, and chemoresistance of cancer cells. A PDC for CD133 was designed by us, and it consists of CD133 targeting peptide LS-7 (amino acid sequence LQNAPRS), a pH-sensitive linker (succinyl), and a cytotoxic payload, the cytotoxic molecule camptothecin (CPT) with potent toxicity in vivo and in vitro. An antitumor study exhibited that the conjugate LS-7-CPT has not only improved its cytotoxicity in tumor cells but also retained its anticancer effect in vivo. In addition, the acute toxicity in mice of LS-7-CPT has been improved and the maximum tolerated dose has been increased by at least 56.2-fold. Pull-down and in vivo fluorescent imaging results indicated that LS-7-CPT was enriched in mice tumors by targeting CD133 protein. As far as we know, this is the first report for a PDC molecule designed for CD133, which is important for the study of CPT drug development.
研究领域:
肿瘤学
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药学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
STAR Protocols
·
2024
·
IF 1.3
Yuanyan Wei,Shuting Geng,Qihang Chen,Jiayue Chen,Zhijun Fan,Yi Li,Yu Si,Yuerong Yang,Ziwei Liang,Jianhai Jiang
Summary CD133 is widely used as a marker to isolate cancer stem cells (CSCs). However, the structural ambiguity of N-glycan of CD133 limits its application in the isolation of CSCs. Here, we present a protocol to sort CSCs from tumor samples by combining CD133 with α-1,2-high-mannose type glycan chains. We describe steps for purifying and biotinylating cyanovirin-N (CVN) proteins and sorting tumor cells and CD133 + α-1,2-Man + (α-1,2-linked mannose + ) cells to provide more specific markers for CSCs. For complete details on the use and execution of this protocol, please refer to Wei et al. 1
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 8
·2209-2218
·
IF 5.831
Siqi Wang,Wenzhi Ren,Jianhua Wang,Zhenqi Jiang,Madiha Saeed,Lili Zhang,Aiguo Li,Aiguo Wu
At present, transmembrane glycoprotein CD133 highly expressed pancreatic cancer stem cells (PCSCs), with the features of chemotherapeutic/radiotherapeutic resistance and exclusive tumorigenic potential, are considered as the primary cause of metastasis and recurrence in pancreatic cancer, and therefore are an effective target in the disease treatment. Furthermore, with the launch of precision medicine, multifunctional nanoprobes have been applied as an efficient strategy for the magnetic resonance imaging (MRI)-guided photothermal therapy (PTT) of pancreatic cancer. In this research, with the aim of achieving precise MRI-guided PTT in CD133 highly expressed PCSCs, novel bTiO2-Gd-CD133mAb nanoprobes were designed and successfully prepared by loading Gd-DOTA and CD133 monoclonal antibodies on black TiO2 nanoparticles. It was very interesting to find that the r1 relaxivity value of the nanoprobes was 34.394 mM−1 s−1, about 7.5 times that of commercial Magnevist (4.5624 mM−1 s−1), which indicates that the nanoprobes have good potential as MRI T1 contrast agents with excellent performance. Herein, CD133 highly expressed PANC-1 cells were selected and verified as PCSCs model. In vitro experiments demonstrated that the nanoprobes exhibited active-targeting ability in PANC-1 cells, and consequently could specially enhance T1-weighted MR imaging and 808 nm near-infrared (NIR)-triggered PTT efficiency in the PCSCs model. Our study not only provides a new strategy for the effective treatment of pancreatic cancer and its’ stem cells, but also further broadens the application of black TiO2 in the field of cancer theranostics.
研究领域:
癌症研究
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纳米技术
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医学成像
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诊疗一体化
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Yiyuan Duan,Shan Yu,Peifang Xu,Xuemei Wang,Xue Feng,Zhengwei Mao,Changyou Gao
Capture of endothelial progenitor cells (EPCs) in situ has been considered as a promising strategy for the rapid endothelialization and long-term patency of artificial blood vessels and implant devices. In this study, a CD133 + EPC capture surface was fabricated by grafting CD133 antibody (a more specific EPC surface marker than CD34) and Arg-Glu-Asp-Val (REDV) peptideon the methacrylate-grafted hyaluronic acid (MA-HA) and heparin-hybridized (MA-HA&Heparin) resisting layer. Vascular endothelial growth factor (VEGF) was further conjugated to the immobilized heparin. This engineered surface showed good hemocompatibility and significantly higher ability of capturing CD133 + EPCs from human peripheral blood mononuclear cells (PBMCs) and obviously upregulated the expression of endothelial cell (EC) marker genes of EPCs such as VEGF receptor 2 (VEGFR2), CD31 , VE-cadherin, and von Willebrand factor (vWF), facilitating the differentiation of EPCs into ECs. The dramatically enhanced EPC proliferation on this surface was dependent on the integrin-VEGFR synergistic signaling, as ERK1/2 phosphorylation was only significantly enhanced on the REDV and VEGF co-immobilized surface. This study highlights a new surface coating strategy for blood-contact materials based on the specific EPC capturing and rapid endothelialization. Statement of Significance Capture of endothelial progenitor cells (EPCs) in situ is a promising strategy for the rapid endothelialization and long-term patency of artificial blood vessels and scaffolds. More specific capture of EPCs by targeting CD133 rather than CD34 can better reduce the risk of inflammation and restenosis. On the other hand, an appropriate microenvironment for EPC proliferation is equally important for endothelialization, which is rarely considered by the existing EPC capture strategies. In this study, the capture ratio of EPCs was significantly increased by simultaneously grafting CD133 antibody and VEGF on a MA-HA and heparin-hybridized antifouling layer. Further, proliferation of EPCs after capture was significantly promoted by grafting VEGF and REDV peptide through the integrin–VEGFR synergistic signaling. This study highlights a new strategy for the surface coating of blood-contact materials based on specific EPC capture and rapid endothelialization.
研究领域:
生物医学工程
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组织工程
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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
ACS Biomaterials Science & Engineering
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2021
·
IF 4.749
Lv Jianghong,Meng Tingting,Zeng Yingping,Yu Tong,Zhao Lanxia,Liu Jingwen,Zhou Wentao,Chen Pengbo,Yuan Hong,Hu Fuqiang
Hepatocellular carcinoma (HCC) is known as the most common malignancy of the hepatobiliary system with a continued increase in incidence but limited therapeutic options. Nanomedicine has provided a promising strategy through engineered nanocarriers that are capable of targeting therapeutic agents specifically to tumor cells. In this research, two aptamer/peptide-modified lipid-based drug delivery systems (A54-PEG-SLN/OXA and A15-PEG-SLN/SAL) were developed as a sequential therapeutic strategy to conquer specific hepatocellular carcinoma. The nanomedicine A54-PEG-SLN/OXA was able to target specific hepatocellular carcinoma cell BEL-7402 and exhibited a strong targeting ability and antitumor efficiency both in vitro and in vivo. The A15-PEG-SLN/SAL could target and penetrate deeply to the spheroid composed of CD133+ cancer cells. In the study of developing a sequential therapeutic strategy, we demonstrated that A54-PEG-SLN/OXA could kill tumor cells and expose CD133+ cancer cells. After the administration of A15-PEG-SLN/SAL, the growth of the tumors was significantly inhibited. In conclusion, the aptamer/peptide-modified lipid-based drug delivery systems, A54-PEG-SLN/OXA and A15-PEG-SLN/SAL, could specifically target carcinoma cells and had an evident antitumor effect when administrated sequentially.
研究领域:
肿瘤学
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药剂学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EMBO Molecular Medicine
·
2025
·
IF 8.3
HouYibo,WangZixian,WangWenlin,TangQing,CaiYongde,YuSiyang,WangJin,YanXiu,WangGuocai,LobiePeter E,ZhangYubo,DaiXiaoyong,MaShaohua
Advanced algorithms have significantly improved the efficiency of in vitro screening for protein-interactive compounds. However, target antigen (TAA/TSA)-based drug discovery remains challenging, as predictions of compound-protein interaction (CPI) based solely on molecular structure fail to fully elucidate the underlying mechanisms. In this study, we utilized deep learning, specifically TransformerCPI to screen active molecules from a Chinese herb compound library based on protein sequences. Two natural products, Polyphyllin V and Polyphyllin H, were identified as targeting the pan-cancer marker CD133. Their anti-tumor efficacy and safety were confirmed across validation in cancer cell lines, tumor patient-derived organoids, and animal models. Despite their analogous structures and binding affinity to CD133, Polyphyllin V suppresses the PI3K-AKT pathway, inducing pyroptosis and blockage of mitophagy, whereas Polyphyllin H inhibits the Wnt/β-catenin pathway and triggers apoptosis. These distinct mechanisms underscore the potential of combining AI-driven screening with biological validation. This AI-to-patient pipeline identifies Polyphyllin V and Polyphyllin H as CD133-targeted drugs for pan-cancer therapy, and reveals the limitations of virtual screening alone and emphasizes the necessity of live model evaluation in AI-based therapeutic discovery.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2026
·
IF 13.6
Kaiwei Xu,Chaoxiang Xie,Ruoyu Wu,Jiayong Luo,Yonglong Ye,Yunhao Zhang,Mingrui Song,Mingchao Xue,Ao Zeng,Wenzhi Ren,Aiguo Wu,Jianhua Wang
Ferroptosis has emerged as a promising strategy for treating refractory malignancies such as pancreatic ductal adenocarcinoma (PDAC), but its efficacy is limited by multilayered resistance, including classical tumor-intrinsic pathways and a recently identified cancer-associated fibroblast (CAF) bypass mediated by the TGFβ1-Cys-GSH axis. Most studies have focused on cancer cell-intrinsic mechanisms, leaving ferroptosis-based therapy for PDAC suboptimal. To address this challenge, we propose a dual-pathway blockade that simultaneously targets both the intrinsic cancer cell pathway and the CAF-mediated exogenous pathway. We developed a multifunctional theranostic nanoplatform (MEC), consisting of a manganese–porphyrin metal-organic framework (MOF) loaded with Erastin and surface-modified with an anti-CD133 monoclonal antibody (CD133 mAb) for targeted delivery. In combination with Repsox, MEC disrupts the cysteine exchange cascade between cancer cells and fibroblasts, thereby depleting intracellular glutathione (GSH), enhancing reactive oxygen species (ROS) generation through TCPP-mediated sonodynamic and Mn-driven Fenton-like reactions, and inducing lipid peroxidation-dependent ferroptosis in PDAC cells. Moreover, MEC offers dual-modality magnetic resonance-fluorescence imaging to noninvasively visualize intratumoral GSH dynamics, enabling treatment optimization and precise therapeutic response assessment. Collectively, this study establishes a comprehensive strategy to overcome ferroptosis resistance in pancreatic cancer and introduces a multifunctional theranostic nanoplatform with potential for effective PDAC management.
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DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Ding Jie,Xu Weiqiang,Tan Jing,Liu Zhifang,Huang Guoliang,Wang Shoushan,He Zhiwei
Antigen CD133 is a glycoprotein present on the surface of cancer stem cells (CSCs), which is a key molecule to regulate the fate of stem cells and a functional marker of stem cells. Herein, a novel fluorescence “turn-on” nano-aptamer sensor for quantifying CD133 was designed using hybridization between CD133-targeted aptamers and partially complementary paired RNA (ssRNA), which were modified on the surface of quantum dots (QDs) and gold nanoparticles (AuNPs), respectively. Owing to the hybridization of aptamers and ssRNA, the distance between QDs and AuNPs was shortened, which caused fluorescence resonance energy transfer (FRET) between them, and the florescence of QDs was quenched by AuNPs. When CD133 competitively replaced ssRNA and was bound to aptamers, AuNPs-ssRNA could be released, which led to a recovery of fluorescent signals of QDs. The increase in the relative value of fluorescence intensity was investigated to linearly correlate with the CD133 concentration in the range of 0–1.539 μM, and the detection limit was 6.99 nM. In confocal images of A549 cells, the CD133 aptamer sensor was further proved applicable in lung cancer cell samples with specificity, precision, and accuracy. Compared with complicated methods, this study provided a fresh approach to develop a highly sensitive and selective detection sensor for CSC markers.
研究领域:
生物医学工程
·
分子生物学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2013
·
IF 5.008
Shuyang Lu,Peng Zhang,Xiaoning Sun,Feirong Gong,Shouguo Yang,Li Shen,Zheyong Huang,Chunsheng Wang
An anti-CD133 antibody multilayer functionalized by heparin/collagen on an expanded polytetrafluoroethylene (ePTFE) graft was developed to accelerate early endothelialization. The surface modification of ePTFE grafts demonstrated that the multilayer is stable in static incubation and shaking conditions and that the anti-CD133 antibodies were successfully cross-linked onto the surface. Blood compatibility tests revealed that the coimmobilized heparin/collagen films in the presence or absence of anti-CD133 antibodies prolonged the blood coagulation time and that there was less platelet activation and aggregation, whereas the hemolysis rate was comparable with the bare ePTFE grafts. Cellular proliferation was not inhibited, as the heparin/collagen synthetic vascular grafts coated with CD133 antibody showed little cytotoxicity. The endothelial cells adhered well to the modified ePTFE grafts during a cell adhesion assay. A porcine carotid artery transplantation model was used to evaluate the modified ePTFE grafts in vivo. The results of histopathological staining and scanning electron microscopy indicated that the anti-CD133 antibody was able to accelerate the attachment of vascular endothelial cells onto the ePTFE grafts, resulting in early rapid endothelialization. The success of the anti-CD133 antibody-functionalized heparin/collagen multilayer will provide an effective selection system for the surface modification of synthetic vascular grafts and improve their use in clinical applications.
研究领域:
生物材料
·
组织工程
·
血管外科
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DOI
PubMed
高影响因子
Materials Today Communications
·
2025
·
IF 4.5
Ziru Sun,Enxiang Jiao,Chengchen Deng,Meihong Xu,Jinglan He,Peizhao Shi,Xiaoguang Lin,Sai Chen,Yuanbiao Liu,Kai Guo,Xiaowei Li,Kun Li,Lebing Chang,Huimin Wang,Xuehai Zhang,Yuechuan Li,Duanqiang Xiao,Xiaoshan Cui,Guiying Li,Jiao Li,Haijun Zhang
Long-term patency remains the main challenge for small-diameter vascular grafts in clinical applications. In addition to anticoagulation and endothelialization, antiproliferative treatment of the autologous vessels at the suture site and mechanical compatibility are also important influences on long-term patency rates. In order to address these issues simultaneously, this study constructed a functionally segmented small-diameter vascular graft with anticoagulant and endothelialization functions in the whole-graft and antiproliferation functions at both ends by emulsion electrospinning. The functionally segmented vascular grafts were composed of thermoplastic polyurethane (TPU) and Type I collagen (Col), with heparin (Hep)/anti-CD133 antibody in the whole segment and rapamycin (RAPA) loaded at both ends. In addition，through component modulation, we prepared blood vessels possessing excellent mechanical matching with human autologous blood vessels, which is highly conducive to enhance the stability of blood vessels and promote endothelialization growth. Moreover, compared with the TPU group, the thermoplastic polyurethane/collagen/heparin/anti-CD133 antibody/rapamycin (TCHCR) group showed better biocompatibility and hemocompatibility. In vivo implantation experiments in the New Zealand Great White Rabbit have shown that the TCHCR group exhibited good anticoagulant, endothelialization and antiproliferative effects. Therefore，the functionally segmented vascular grafts we prepared may succeed in solving the problem of vascular long-term patency rates.
研究领域:
生物材料
·
组织工程
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生物医学工程
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血管外科
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纳米制造
·
药物递送
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产品关联
DOI
高影响因子
DRUG DELIVERY
·
2017
·
IF 6.402
Wei Chen,Lin Li,Xiaofen Zhang,Yuan Liang,Zhijun Pu,Lingfeng Wang,Jingxin Mo
Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease with no approved targeted therapy. Curcumin has shown therapeutic potential against TNBC, but it shows low bioavailability and low efficacy when administered as a free drug. Here we describe a novel vehicle for in vivo delivery of curcumin based on the phosphorylated calixarene POCA4C6. Curcumin-loaded POCA4C6 micelles (CPM) were prepared using the thin-film method and they showed a unilamellar structure with an average particle size of 3.86 nm. The micelles showed high curcumin encapsulation efficiency and loading was based on liquid chromatography-tandem mass spectrometry. Studies with cell cultures suggest that CPM can sustainably release curcumin in a pH-dependent manner. The micelles efficiently inhibited proliferation, invasion, migration and tumor spheroid formation by BT-549 human breast cancer cells. These effects involved increased apoptosis and reduced levels of nuclear β-catenin and androgen receptor. After injection into tumor xenografts, CPM persisted in the tumor tissue and efficiently inhibited tumor growth without causing obvious systemic toxicity. CPM also significantly reduced levels of CD44+/CD133+ breast cancer stem cells. Our results highlight the potential of CPM as an effective therapy against TNBC.
研究领域:
肿瘤学
·
药剂学
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药物递送系统
·
癌症干细胞
✓ 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）