The Experts below are selected from a list of 732 Experts worldwide ranked by ideXlab platform
Miqin Zhang - One of the best experts on this subject based on the ideXlab platform.
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Gemcitabine and Chlorotoxin conjugated iron oxide nanoparticles for glioblastoma therapy
Journal of materials chemistry. B, 2015Co-Authors: Guanyou Lin, Victoria K. Patton, Kui Wang, Oliver W. Press, Miqin ZhangAbstract:Many small-molecule anti-cancer drugs have short blood half-lives and toxicity issues due to non-specificity. Nanotechnology has shown great promise in addressing these issues. Here, we report the development of an anti-cancer drug gemcitabine-conjugated iron oxide nanoparticle for glioblastoma therapy. A glioblastoma targeting peptide, Chlorotoxin, was attached after drug conjugation. The nanoparticle has a small size (~32 nm) and uniform size distribution (PDI ≈ 0.1), and is stable in biological medium. The nanoparticle effectively enter cancer cells without losing potency compared to free drug. Significantly, the nanoparticle showed a prolonged blood half-life and the ability to cross the blood-brain barrier in wild type mice.
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Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma.
ACS nano, 2010Co-Authors: Forrest M. Kievit, Chen Fang, Omid Veiseh, Narayan Bhattarai, Dong-hoon Lee, Richard G. Ellenbogen, Miqin ZhangAbstract:Glioma accounts for 80% of brain tumors and currently remains one of the most lethal forms of cancers. Gene therapy could potentially improve the dismal prognosis of patients with glioma, but this treatment modality has not yet reached the bedside from the laboratory due to the lack of safe and effective gene delivery vehicles. In this study we investigate targeted gene delivery to C6 glioma cells in a xenograft mouse model using Chlorotoxin (CTX) labeled nanoparticles. The developed nanovector consists of an iron oxide nanoparticle core, coated with a copolymer of chitosan, polyethylene glycol (PEG), and polyethylenimine (PEI). Green fluorescent protein (GFP) encoding DNA was bound to these nanoparticles, and CTX was then attached using a short PEG linker. Nanoparticles without CTX were also prepared as a control. Mice bearing C6 xenograft tumors were injected intravenously with the DNA-bound nanoparticles. Nanoparticle accumulation in the tumor site was monitored using magnetic resonance imaging and ana...
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Functionalization of iron oxide magnetic nanoparticles with targeting ligands: their physicochemical properties and in vivo behavior
Nanomedicine (London England), 2010Co-Authors: Chen Fang, Omid Veiseh, Forrest M. Kievit, Narayan Bhattarai, Freddy Y. Wang, Zach Stephen, Dong-hoon Lee, Richard G. Ellenbogen, Miqin ZhangAbstract:Aim: To develop and evaluate two tumor-specific nanoprobes by functionalization of a polyethylene glycol-immobilized nanoparticle with arginine–glycine–aspartic acid (RGD) or Chlorotoxin ligand that targets αvβ3 integrin and matrix metalloproteinase-2 receptors, respectively. Materials & methods: The nanoprobes were made of iron oxide cores, biocompatible polymer coating, and surface-conjugated RGD or Chlorotoxin peptide. The tumor-targeting specificity of the nanoprobes was evaluated both in vitro and in vivo. Results & discussion: Both nanoprobes were highly dispersive and exhibited excellent long-term stability in cell culture media. The RGD-conjugated nanoprobe displayed a strong initial accumulation near neovasculatures in tumors followed by quick clearance. Conversely, the Chlorotoxin-enabled nanoprobe exhibited sustained accumulation throughout the tumor. Conclusion: These findings revealed the influence of the targeting ligands on the intratumoral distribution of the ligand-enabled nanoprobes. Wit...
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inhibition of tumor cell invasion with Chlorotoxin bound superparamagnetic nanoparticles
Small, 2008Co-Authors: Omid Veiseh, Chen Fang, Forrest M. Kievit, Jonathan Gunn, Miqin ZhangAbstract:Nanoparticles have been investigated as drug delivery vehicles, contrast agents, and multifunctional devices for patient care. Current nanoparticle-based therapeutic strategies for cancer treatment have been mainly based on delivery of chemotherapeutic agents to induce apoptosis or DNA/siRNA to regulate oncogene expression. Here, we present a nanoparticle system that demonstrates an alternative approach to the treatment of cancers, through the inhibition of cell invasion, while serving as a magnetic resonance and optical imaging contrast agent. The nanoparticle is comprised of an iron oxide nanoparticle core, conjugated with an amine-functionalized PEG silane and a small peptide, Chlorotoxin (CTX), which enables the tumor cell-specific binding of the nanoparticle. We show that the nanoparticle exhibits substantially enhanced cellular uptake and an invasion inhibition rate of ~98% compared to unbound CTX (~45%). Significantly, our investigation from flow cytometry analysis, transmission electron microscopy and fluorescent imaging revealed that the CTX-enabled nanoparticles deactivated the membrane-bound matrix metalloproteinase 2 (MMP-2) and induced increased internalization of lipid rafts that contain surface-expressed MMP-2 and volume-regulating ion channels through receptor-mediated endocytosis, leading to enhanced prohibitory effects. Since upregulation and activity of MMP-2 have been observed in tumors of neuroectodermal origin, and in cancers of the breast, colon, skin, lung, prostate, ovaries and a host of others, this nanoparticle system can be potentially used for non-invasive diagnosis and treatment of a variety of cancer types.
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Tumor-targeted drug delivery and MRI contrast enhancement by Chlorotoxin-conjugated iron oxide nanoparticles.
Nanomedicine (London England), 2008Co-Authors: Conroy Sun, Stacey Hansen, James M Olson, Chen Fang, Omid Veiseh, Dong-hoon Lee, Richard G. Ellenbogen, Zachary R. Stephen, Miqin ZhangAbstract:Aims: This study examines the capabilities of an actively targeting superparamagnetic nanoparticle to specifically deliver therapeutic and MRI contrast agents to cancer cells. Materials & methods: Iron oxide nanoparticles were synthesized and conjugated to both a chemotherapeutic agent, methotrexate, and a targeting ligand, Chlorotoxin, through a poly(ethylene glycol) linker. Cytotoxicity of this nanoparticle conjugate was evaluated by Alamar Blue cell viability assays, while tumor-cell specificity was examined in vitro and in vivo by MRI. Results & discussion: Characterization of these multifunctional nanoparticles confirms the successful attachment of both drug and targeting ligands. The targeting nanoparticle demonstrated preferential accumulation and increased cytotoxicity in tumor cells. Furthermore, prolonged retention of these nanoparticles was observed within tumors in vivo. Conclusion: The improved specificity, extended particle retention and increased cytotoxicity toward tumor cells demonstrated...
Jinhua Zhao - One of the best experts on this subject based on the ideXlab platform.
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A novel Buthus martensii Karsch Chlorotoxin derivative for glioma SPECT imaging
New Journal of Chemistry, 2020Co-Authors: Lingzhou Zhao, Wenli Qiao, Jingyi Zhu, Tiantian Wang, Changcun Liu, Ningning Song, Jiqin Yang, Meilin Zhu, Jinhua ZhaoAbstract:An increasing number of studies show the diagnostic and therapeutic potential of scorpion venoms and toxins in cancer, including malignant glioma that represents the most fatal primary brain tumors. Chlorotoxin (CTX) and a CTX-like peptide Buthus martensii Karsch Chlorotoxin (BmK CT) derived from scorpion venoms, have been identified as glioma-specific agents for imaging and therapy. In this study, we designed and manufactured a new BmK CT derivative (BmK CT-D) according to the amino acid sequences of native CTX and BmK CT and investigated the possibility of 99mTc-labeled BmK CT-D as a single-positron emission computed tomography (SPECT) imaging agent for glioma diagnosis. The data indicated that the BmK CT-D peptide had good cytocompatibility, improved cellular uptake compared to BmK CT, and could be readily radiolabeled by 99mTc via99mTc-tricarbonyl chemistry with high radiochemical yield and stability in vitro. Moreover, the formed 99mTc-BmK CT-D was able to be used as a probe for SPECT imaging of glioma cells in vitro and in tumor-bearing mice in vivo, indicating that the designed peptide is a promising targeting agent for tumor imaging.
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Biological evaluation of [ 99m Tc]Tc-labeled Buthus martensii Karsch Chlorotoxin peptide for glioma imaging
Journal of Radioanalytical and Nuclear Chemistry, 2020Co-Authors: Changcun Liu, Lingzhou Zhao, Wenli Qiao, Tiantian Wang, Jiqin Yang, Meilin Zhu, Jinhua ZhaoAbstract:This study was to investigate the synthesis and biological evaluation of [99mTc]Tc-labeled Buthus martensii Karsch Chlorotoxin ([99mTc]Tc-BmK CT) as a radiopharmaceutical for glioma single photon computed emission tomography (SPECT) imaging. The results showed that BmK CT peptide modified with a hexahistidine tag displayed good cytocompatibility in vitro, and could be efficiently radiolabeled with 99mTc via [99mTc]Tc-tricarbonyl chemistry. The [99mTc]Tc-BmK CT showed satisfactory radiochemical purity and stability in vitro, and could be developed as a probe for targeted SPECT imaging of glioma cells in vitro and in a tumor-bearing mouse model. Our data indicated that the synthesized [99mTc]Tc-BmK CT might be developed as a promising imaging agent for glioma diagnostic application.
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BmK CT and 125I-BmK CT suppress the invasion of glioma cells in vitro via matrix metalloproteinase-2.
Molecular medicine reports, 2017Co-Authors: Na Sun, Lingzhou Zhao, Wenli Qiao, Yan Xing, Jinhua ZhaoAbstract:Chlorotoxin (CTX) is an established blocker of small‑conductance Cl‑ channels and has previously been demonstrated to inhibit the invasion of glioma cells. Buthus martensii Karsch Chlorotoxin‑like toxin (BmK CT) is the first Chlorotoxin-like peptide. The present study aimed to determine the inhibitory effect of BmK CT on the invasive ability of glioma cells, using a Transwell assay. BmK CT was subsequently radiolabeled with radionuclide 125I and its activity was compared with BmK CT. Additionally, the underlying anti‑invasive mechanism of BmK CT and 125I‑BmK CT on glioma cells was investigated by ELISA and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). It was revealed that BmK CT and 125I‑BmK CT were able to inhibit the invasion of glioma cells and that 125I‑BmK CT was superior to BmK CT. Consistent with the results of the Transwell assay, matrix metalloproteinase‑2 (MMP‑2) secretion by glioma cells was significantly reduced following treatment with BmK CT or 125I‑BmK CT (P 0.05). In conclusion, the present study demonstrated that BmK CT and 125I‑BmK CT reduced the invasion of glioma cells via downregulation of MMP-2 expression. However, inhibition of the invasion of glioma cells was not demonstrated at the mRNA level.
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Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas.
ACS applied materials & interfaces, 2015Co-Authors: Lingzhou Zhao, Yongjun Cheng, Jingyi Zhu, Zhijuan Xiong, Yueqin Tang, Lilei Guo, Xiangyang Shi, Jinhua ZhaoAbstract:Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide 131I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation five amine-terminated poly(amidoamine) dendrimers were used as a platform to be sequentially conjugated with polyethylene glycol (PEG), targeting agent Chlorotoxin (CTX), and 3-(4′-hydroxyphenyl)propionic acid-OSu (HPAO). This was followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I to form the targeted theranostic dendrimeric nanoplatform. We show that the dendrimer platform possessing approximately 7.7 CTX and 21.1 HPAO moieties on each dendrimer displays excellent cytocompatibility in a given concentration range (0–20 μM) and can specifically target cancer cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX. With the attached HPAO moiety having the phenol group, the dendrimer platform can be effectively...
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Chlorotoxin-conjugated nanoparticles for targeted imaging and therapy of glioma.
Current topics in medicinal chemistry, 2015Co-Authors: Lingzhou Zhao, Xiangyang Shi, Jinhua ZhaoAbstract:This review reports the recent advances in Chlorotoxin (CTX)-targeted nanoparticles (NPs) for imaging and therapy of glioma. CTX has been identified as a targeting ligand to specifically bind to glioma. Through different conjugation approaches, CTX can be conjugated onto iron oxide NPs, quantum dots, and rare-earth upconversion NPs for targeted magnetic resonance and fluorescence imaging of glioma. Likewise, CTX-conjugated NPs can also be used as a carrier system to load anticancer drugs or therapeutic genes for targeted chemotherapy or gene therapy of glioma, respectively. Some of the key developments in this area of research will be introduced in detail. Challenges and future perspectives in the development of CTX-conjugated NPs will be discussed.
Ying Wang - One of the best experts on this subject based on the ideXlab platform.
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Chlorotoxin targets erα vasp signaling pathway to combat breast cancer
Cancer Medicine, 2019Co-Authors: Ying Wang, Song Han, Yihao Tian, Wenting Pan, Yang Gao, Zun Zhang, Jingwei Zhang, Lei WeiAbstract:Breast cancer is one of the most common malignant tumors among women worldwide. About 70-75% of primary breast cancers belong to estrogen receptor (ER)-positive breast cancer. In the development of ER-positive breast cancer, abnormal activation of the ERα pathway plays an important role and is also a key point leading to the failure of clinical endocrine therapy. In this study, we found that the small molecule peptide Chlorotoxin (CTX) can significantly inhibit the proliferation, migration and invasion of breast cancer cells. In in vitro study, CTX inhibits the expression of ERα in breast cancer cells. Further studies showed that CTX can directly bind to ERα and change the protein secondary structure of its LBD domain, thereby inhibiting the ERα signaling pathway. In addition, we also found that vasodilator stimulated phosphoprotein (VASP) is a target gene of ERα signaling pathway, and CTX can inhibit breast cancer cell proliferation, migration, and invasion through ERα/VASP signaling pathway. In in vivo study, CTX significantly inhibits growth of ER overexpressing breast tumor and, more importantly, based on the mechanism of CTX interacting with ERα, we found that CTX can target ER overexpressing breast tumors in vivo. Our study reveals a new mechanism of CTX anti-ER-positive breast cancer, which also provides an important reference for the study of CTX anti-ER-related tumors.
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Chlorotoxin targets ERα/VASP signaling pathway to combat breast cancer
Cancer medicine, 2019Co-Authors: Ying Wang, Song Han, Yihao Tian, Wenting Pan, Yang Gao, Zun ZhangAbstract:Breast cancer is one of the most common malignant tumors among women worldwide. About 70-75% of primary breast cancers belong to estrogen receptor (ER)-positive breast cancer. In the development of ER-positive breast cancer, abnormal activation of the ERα pathway plays an important role and is also a key point leading to the failure of clinical endocrine therapy. In this study, we found that the small molecule peptide Chlorotoxin (CTX) can significantly inhibit the proliferation, migration and invasion of breast cancer cells. In in vitro study, CTX inhibits the expression of ERα in breast cancer cells. Further studies showed that CTX can directly bind to ERα and change the protein secondary structure of its LBD domain, thereby inhibiting the ERα signaling pathway. In addition, we also found that vasodilator stimulated phosphoprotein (VASP) is a target gene of ERα signaling pathway, and CTX can inhibit breast cancer cell proliferation, migration, and invasion through ERα/VASP signaling pathway. In in vivo study, CTX significantly inhibits growth of ER overexpressing breast tumor and, more importantly, based on the mechanism of CTX interacting with ERα, we found that CTX can target ER overexpressing breast tumors in vivo. Our study reveals a new mechanism of CTX anti-ER-positive breast cancer, which also provides an important reference for the study of CTX anti-ER-related tumors.
George P Studzinski - One of the best experts on this subject based on the ideXlab platform.
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the disparate effects of mek specific inhibitors pd09059 and u0126 on1 25d3 induced differentiation of hl60 cells
Cancer Research, 2005Co-Authors: Jing Zhang, Xuening Wang, George P StudzinskiAbstract:5520 Chlorotoxin, also called TM-601, is a 36-amino acid peptide originally derived from the venom of the Giant Israeli scorpion Leiurus quinquestriatus. In previous studies, Chlorotoxin appeared to bind specifically to glioblastoma cell lines and glioblastoma sections, but not to normal brain tissue, and tumor-specific binding was later extended to neuroectodermal tissue. In the present study, using colorimetric binding assays, histochemical staining, and FACS analysis, we demonstrate that Chlorotoxin binds to multiple human cancer cell lines and tissues, including solid tumors (glioma, lung, breast, prostate, melanoma, colorectal), as well as hematologic tumor cell lines (leukemia, lymphoma, myeloma). Furthermore, we have dissected the amino acid sequence of Chlorotoxin and demonstrated that there are two distinct binding domains in this small molecule, designated α and β, each capable of binding tumor cells. The specific target and mechanism of action of Chlorotoxin has remained unclear. To address this, multiple human tumor cell lines were used to localize Chlorotoxin binding. In all cell lines tested, Chlorotoxin binding was predominantly localized to cellular lamellipodia, organelles involved in signal transduction, cell invasion, adhesion, and motility. Because membrane phospholipids are crucial regulatory components of intracellular signaling pathways, the ability of Chlorotoxin to bind phosphatidylinositol phosphates was investigated. Using an in vitro binding assay, we illustrate that Chlorotoxin binds multiple phosphatidylinositol isoforms and binds with greatest affinity to phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2), a membrane phospholipid vital to the PI3K-Akt pathway that has been implicated in multiple human cancers. This binding could profoundly affect many cellular functions, including subsequent signal transduction events, cell cycle changes, protein and DNA synthesis, and cell movement. In summary, these data provide solid evidence that Chlorotoxin binds multiple human cancer types, including solid and hematologic tumors, and that the α and β domains of Chlorotoxin facilitate binding of Chlorotoxin to cancer cells through a membrane phosphatidylinositol localized to the lamellipodia of cancer cells. 131I-TM-601, a synthetic version of Chlorotoxin conjugated to a radioisotope of iodine, is currently in Phase II clinical development for the treatment of malignant brain tumors.
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The disparate effects of “MEK-specific” inhibitors PD09059 and U0126 on1,25D3-induced differentiation of HL60 cells
Cancer Research, 2005Co-Authors: Jing Zhang, Xuening Wang, George P StudzinskiAbstract:5520 Chlorotoxin, also called TM-601, is a 36-amino acid peptide originally derived from the venom of the Giant Israeli scorpion Leiurus quinquestriatus. In previous studies, Chlorotoxin appeared to bind specifically to glioblastoma cell lines and glioblastoma sections, but not to normal brain tissue, and tumor-specific binding was later extended to neuroectodermal tissue. In the present study, using colorimetric binding assays, histochemical staining, and FACS analysis, we demonstrate that Chlorotoxin binds to multiple human cancer cell lines and tissues, including solid tumors (glioma, lung, breast, prostate, melanoma, colorectal), as well as hematologic tumor cell lines (leukemia, lymphoma, myeloma). Furthermore, we have dissected the amino acid sequence of Chlorotoxin and demonstrated that there are two distinct binding domains in this small molecule, designated α and β, each capable of binding tumor cells. The specific target and mechanism of action of Chlorotoxin has remained unclear. To address this, multiple human tumor cell lines were used to localize Chlorotoxin binding. In all cell lines tested, Chlorotoxin binding was predominantly localized to cellular lamellipodia, organelles involved in signal transduction, cell invasion, adhesion, and motility. Because membrane phospholipids are crucial regulatory components of intracellular signaling pathways, the ability of Chlorotoxin to bind phosphatidylinositol phosphates was investigated. Using an in vitro binding assay, we illustrate that Chlorotoxin binds multiple phosphatidylinositol isoforms and binds with greatest affinity to phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2), a membrane phospholipid vital to the PI3K-Akt pathway that has been implicated in multiple human cancers. This binding could profoundly affect many cellular functions, including subsequent signal transduction events, cell cycle changes, protein and DNA synthesis, and cell movement. In summary, these data provide solid evidence that Chlorotoxin binds multiple human cancer types, including solid and hematologic tumors, and that the α and β domains of Chlorotoxin facilitate binding of Chlorotoxin to cancer cells through a membrane phosphatidylinositol localized to the lamellipodia of cancer cells. 131I-TM-601, a synthetic version of Chlorotoxin conjugated to a radioisotope of iodine, is currently in Phase II clinical development for the treatment of malignant brain tumors.
Lingzhou Zhao - One of the best experts on this subject based on the ideXlab platform.
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A novel Buthus martensii Karsch Chlorotoxin derivative for glioma SPECT imaging
New Journal of Chemistry, 2020Co-Authors: Lingzhou Zhao, Wenli Qiao, Jingyi Zhu, Tiantian Wang, Changcun Liu, Ningning Song, Jiqin Yang, Meilin Zhu, Jinhua ZhaoAbstract:An increasing number of studies show the diagnostic and therapeutic potential of scorpion venoms and toxins in cancer, including malignant glioma that represents the most fatal primary brain tumors. Chlorotoxin (CTX) and a CTX-like peptide Buthus martensii Karsch Chlorotoxin (BmK CT) derived from scorpion venoms, have been identified as glioma-specific agents for imaging and therapy. In this study, we designed and manufactured a new BmK CT derivative (BmK CT-D) according to the amino acid sequences of native CTX and BmK CT and investigated the possibility of 99mTc-labeled BmK CT-D as a single-positron emission computed tomography (SPECT) imaging agent for glioma diagnosis. The data indicated that the BmK CT-D peptide had good cytocompatibility, improved cellular uptake compared to BmK CT, and could be readily radiolabeled by 99mTc via99mTc-tricarbonyl chemistry with high radiochemical yield and stability in vitro. Moreover, the formed 99mTc-BmK CT-D was able to be used as a probe for SPECT imaging of glioma cells in vitro and in tumor-bearing mice in vivo, indicating that the designed peptide is a promising targeting agent for tumor imaging.
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Biological evaluation of [ 99m Tc]Tc-labeled Buthus martensii Karsch Chlorotoxin peptide for glioma imaging
Journal of Radioanalytical and Nuclear Chemistry, 2020Co-Authors: Changcun Liu, Lingzhou Zhao, Wenli Qiao, Tiantian Wang, Jiqin Yang, Meilin Zhu, Jinhua ZhaoAbstract:This study was to investigate the synthesis and biological evaluation of [99mTc]Tc-labeled Buthus martensii Karsch Chlorotoxin ([99mTc]Tc-BmK CT) as a radiopharmaceutical for glioma single photon computed emission tomography (SPECT) imaging. The results showed that BmK CT peptide modified with a hexahistidine tag displayed good cytocompatibility in vitro, and could be efficiently radiolabeled with 99mTc via [99mTc]Tc-tricarbonyl chemistry. The [99mTc]Tc-BmK CT showed satisfactory radiochemical purity and stability in vitro, and could be developed as a probe for targeted SPECT imaging of glioma cells in vitro and in a tumor-bearing mouse model. Our data indicated that the synthesized [99mTc]Tc-BmK CT might be developed as a promising imaging agent for glioma diagnostic application.
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BmK CT and 125I-BmK CT suppress the invasion of glioma cells in vitro via matrix metalloproteinase-2.
Molecular medicine reports, 2017Co-Authors: Na Sun, Lingzhou Zhao, Wenli Qiao, Yan Xing, Jinhua ZhaoAbstract:Chlorotoxin (CTX) is an established blocker of small‑conductance Cl‑ channels and has previously been demonstrated to inhibit the invasion of glioma cells. Buthus martensii Karsch Chlorotoxin‑like toxin (BmK CT) is the first Chlorotoxin-like peptide. The present study aimed to determine the inhibitory effect of BmK CT on the invasive ability of glioma cells, using a Transwell assay. BmK CT was subsequently radiolabeled with radionuclide 125I and its activity was compared with BmK CT. Additionally, the underlying anti‑invasive mechanism of BmK CT and 125I‑BmK CT on glioma cells was investigated by ELISA and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). It was revealed that BmK CT and 125I‑BmK CT were able to inhibit the invasion of glioma cells and that 125I‑BmK CT was superior to BmK CT. Consistent with the results of the Transwell assay, matrix metalloproteinase‑2 (MMP‑2) secretion by glioma cells was significantly reduced following treatment with BmK CT or 125I‑BmK CT (P 0.05). In conclusion, the present study demonstrated that BmK CT and 125I‑BmK CT reduced the invasion of glioma cells via downregulation of MMP-2 expression. However, inhibition of the invasion of glioma cells was not demonstrated at the mRNA level.
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Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas.
ACS applied materials & interfaces, 2015Co-Authors: Lingzhou Zhao, Yongjun Cheng, Jingyi Zhu, Zhijuan Xiong, Yueqin Tang, Lilei Guo, Xiangyang Shi, Jinhua ZhaoAbstract:Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide 131I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation five amine-terminated poly(amidoamine) dendrimers were used as a platform to be sequentially conjugated with polyethylene glycol (PEG), targeting agent Chlorotoxin (CTX), and 3-(4′-hydroxyphenyl)propionic acid-OSu (HPAO). This was followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I to form the targeted theranostic dendrimeric nanoplatform. We show that the dendrimer platform possessing approximately 7.7 CTX and 21.1 HPAO moieties on each dendrimer displays excellent cytocompatibility in a given concentration range (0–20 μM) and can specifically target cancer cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX. With the attached HPAO moiety having the phenol group, the dendrimer platform can be effectively...
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Chlorotoxin-conjugated nanoparticles for targeted imaging and therapy of glioma.
Current topics in medicinal chemistry, 2015Co-Authors: Lingzhou Zhao, Xiangyang Shi, Jinhua ZhaoAbstract:This review reports the recent advances in Chlorotoxin (CTX)-targeted nanoparticles (NPs) for imaging and therapy of glioma. CTX has been identified as a targeting ligand to specifically bind to glioma. Through different conjugation approaches, CTX can be conjugated onto iron oxide NPs, quantum dots, and rare-earth upconversion NPs for targeted magnetic resonance and fluorescence imaging of glioma. Likewise, CTX-conjugated NPs can also be used as a carrier system to load anticancer drugs or therapeutic genes for targeted chemotherapy or gene therapy of glioma, respectively. Some of the key developments in this area of research will be introduced in detail. Challenges and future perspectives in the development of CTX-conjugated NPs will be discussed.