The Experts below are selected from a list of 33411 Experts worldwide ranked by ideXlab platform
Dong M Shin - One of the best experts on this subject based on the ideXlab platform.
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targeted iron oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer
ACS Nano, 2014Co-Authors: Dongsheng Wang, Baowei Fei, Luma V Halig, Xulei Qin, Zhongliang Hu, Hong Xu, Yongqiang Andrew Wang, Zhengjia Chen, Sungjin Kim, Dong M ShinAbstract:Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer Targeting Ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin β1. Then the PDT drug Pc 4 was successfully encapsulated into the Ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using ...
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detection of circulating tumor cells in human peripheral blood using surface enhanced raman scattering nanoparticles
Cancer Research, 2011Co-Authors: Xu Wang, Ximei Qian, Jonathan J Beitler, Zhuo Georgia Chen, Fadlo R Khuri, Melinda M Lewis, Hyung Ju C Shin, Shuming Nie, Dong M ShinAbstract:The detection and characterization of circulating tumor cells (CTCs) holds great promise for personalizing medicine and optimizing systemic therapy. However, low specificity, low sensitivity and the time consuming nature of current approaches have impeded clinical adoption. Here we report a new method using Surface-Enhanced Raman Spectroscopy (SERS) to directly measure targeted CTCs in the presence of white blood cells. SERS nanoparticles with epidermal growth factor (EGF) peptide as a Targeting Ligand have successfully identified CTCs in the peripheral blood of 19 patients with squamous cell carcinoma of the head and neck (SCCHN), with a range of 1–720 CTCs per milliliter of whole blood. Our technique may provide an important new clinical tool for management of patients with SCCHN and other cancers.
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detection of circulating tumor cells in human peripheral blood using surface enhanced raman scattering nanoparticles
Cancer Research, 2011Co-Authors: Xu Wang, Ximei Qian, Jonathan J Beitler, Zhuo Georgia Chen, Fadlo R Khuri, Melinda M Lewis, Hyung Ju C Shin, Dong M ShinAbstract:The detection and characterization of circulating tumor cells (CTCs) holds great promise for personalizing medicine and optimizing systemic therapy. However, low specificity, low sensitivity and the time consuming nature of current approaches have impeded clinical adoption. Here we report a new method using Surface-Enhanced Raman Spectroscopy (SERS) to directly measure targeted CTCs in the presence of white blood cells. SERS nanoparticles with epidermal growth factor (EGF) peptide as a Targeting Ligand have successfully identified CTCs in the peripheral blood of 19 patients with squamous cell carcinoma of the head and neck (SCCHN), with a range of 1–720 CTCs per milliliter of whole blood. Our technique may provide an important new clinical tool for management of patients with SCCHN and other cancers.
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detection of circulating tumor cells in human peripheral blood using surface enhanced raman scattering nanoparticles
Cancer Research, 2011Co-Authors: Xu Wang, Ximei Qian, Jonathan J Beitler, Zhuo Georgia Chen, Fadlo R Khuri, Melinda M Lewis, Hyung Ju C Shin, Shuming Nie, Dong M ShinAbstract:The detection and characterization of circulating tumor cells (CTC) holds great promise for personalizing medicine and optimizing systemic therapy. However, low specificity, low sensitivity, and the time consuming nature of current approaches have impeded clinical adoption. Here we report a new method using surface-enhanced Raman spectroscopy (SERS) to directly measure targeted CTCs in the presence of white blood cells. SERS nanoparticles with epidermal growth factor peptide as a Targeting Ligand have successfully identified CTCs in the peripheral blood of 19 patients with squamous cell carcinoma of the head and neck (SCCHN), with a range of 1 to 720 CTCs per milliliter of whole blood. Our technique may provide an important new clinical tool for management of patients with SCCHN and other cancers.
Philip S Low - One of the best experts on this subject based on the ideXlab platform.
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Development of a Ligand-Targeted Therapeutic Agent for Neurokinin‑1 Receptor Expressing Cancers
2017Co-Authors: Ananda Kumar Kanduluru, Philip S LowAbstract:The neurokinin-1 receptor (NK1R) plays a significant role in the progression and metastasis of several neuroendocrine tumors. Due to its upregulation in these cancers, NK1R constitutes an attractive receptor for development of Ligand-targeted imaging and therapeutic agents. In this report, we present the design and synthesis of an NK1R Targeting Ligand conjugated to the chemotherapeutic agent, tubulysin B hydrazide (TubBH), via a self-immolative linker. We then explore the ability of this low molecular weight tubulysin conjugate to kill NK1R overexpressing cancer cells both in vitro and in vivo without killing receptor negative healthy cells. Because similar studies in mice bearing NK1-negative tumors reveal no therapeutic impact, we conclude that our NK1R Targeting Ligand is specific for NK1R-expressing cells. Taken together, the data suggest a possible new approach for the treatment of NK1R-positive neuroendocrine cancers
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synthesis and biological analysis of prostate specific membrane antigen targeted anticancer prodrugs
Journal of Medicinal Chemistry, 2010Co-Authors: Sumith A Kularatne, C Venkatesh, Harikrishna R Santhapuram, Kevin Wang, Balasubramanian Vaitilingam, Walter A Henne, Philip S LowAbstract:Ligand-targeted therapeutics have increased in prominence because of their potential for improved potency and reduced toxicity. However, with the advent of personalized medicine, a need for greater versatility in Ligand-targeted drug design has emerged, where each tumor-Targeting Ligand should be capable of delivering a variety of therapeutic agents to the same tumor, each therapeutic agent being selected for its activity on a specific patient's cancer. In this report, we describe the use of a prostate-specific membrane antigen (PSMA)-Targeting Ligand to deliver multiple unrelated cytotoxic drugs to human prostate cancer (LNCaP) cells. We demonstrate that the PSMA-specific Ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid, is capable of mediating the targeted killing of LNCaP cells with many different therapeutic warheads. These results suggest that flexibility can be designed into Ligand-targeted therapeutics, enabling adaptation of a single Targeting Ligand for the treatment of patients with...
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folate receptor mediated drug Targeting from therapeutics to diagnostics
Journal of Pharmaceutical Sciences, 2005Co-Authors: Andrew Richard Hilgenbrink, Philip S LowAbstract:Folate targeted drug delivery has emerged as an alternative therapy for the treatment and imaging of many cancers and inflammatory diseases. Due to its small molecular size and high binding affinity for cell surface folate receptors (FR), folate conjugates have the ability to deliver a variety of molecular complexes to pathologic cells without causing harm to normal tissues. Complexes that have been successfully delivered to FR expressing cells, to date, include protein toxins, immune stimulants, chemotherapeutic agents, liposomes, nanoparticles, and imaging agents. This review will summarize the applications of folic acid as a Targeting Ligand and highlight the various methods being developed for delivery of therapeutic and imaging agents to FR-expressing cells.
Ernst Wagner - One of the best experts on this subject based on the ideXlab platform.
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tuning nanoparticle uptake live cell imaging reveals two distinct endocytosis mechanisms mediated by natural and artificial egfr Targeting Ligand
Nano Letters, 2012Co-Authors: Frauke Martina Mickler, Leonhard Mockl, Nadia Ruthardt, Manfred Ogris, Ernst Wagner, Christoph BrauchleAbstract:Therapeutic nanoparticles can be directed to cancer cells by incorporating selective Targeting Ligands. Here, we investigate the epidermal growth factor receptor (EGFR)-mediated endocytosis of gene carriers (polyplexes) either targeted with natural EGF or GE11, a short synthetic EGFR-binding peptide. Highly sensitive live-cell fluorescence microcopy with single particle resolution unraveled the existence of two different uptake mechanisms; EGF triggers accelerated nanoparticle endocytosis due to its dual active role in receptor binding and signaling activation. For GE11, an alternative EGFR signaling independent, actin-driven pathway is presented.
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defined folate peg sirna conjugates for receptor specific gene silencing
Molecular therapy. Nucleic acids, 2012Co-Authors: Christian Dohmen, Thomas Frohlich, Ulrich Lachelt, Ingo Rohl, Hanspeter Vornlocher, Philipp Hadwiger, Ernst WagnerAbstract:Gene silencing mediated by small interfering RNA (siRNA) is a novel approach in the development of new cancer therapeutics. Polycations used for nucleic acid delivery still remain heterogeneous compounds, despite continuous progress in polymer synthetic technologies. Here we report the development of a structural defined folic acid polyethylene glycol (PEG) siRNA conjugate accessible via click chemistry yielding a monodisperse Ligand-PEG-siRNA conjugate. The folic acid Targeting Ligand was synthesized by solid phase supported peptide chemistry. The conjugate was shown to be specifically internalized into folic acid receptor expressing cells. When combined with a structurally defined polycation, again synthesized with the precision of solid phase chemistry, efficient receptor specific gene silencing is achieved.
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poly i c mediated tumor growth suppression in egf receptor overexpressing tumors using egf polyethylene glycol linear polyethylenimine as carrier
Pharmaceutical Research, 2011Co-Authors: David Schaffert, Manfred Ogris, Melinda Kiss, Wolfgang Rodl, Alexei Shir, Alexander Levitzki, Ernst WagnerAbstract:Purpose To develop a novel polyethylenimine (PEI)-based polymeric carrier for tumor-targeted delivery of cytotoxic double-stranded RNA polyinosinic:polycytidylic acid, poly(I:C). The novel carrier should be chemically less complex but at least as effective as a previously developed tetra-conjugate containing epidermal growth factor (EGF) as Targeting Ligand, polyethylene glycol (PEG) as shielding spacer, 25 kDa branched PEI as RNA binding and endosomal buffering agent, and melittin as endosomal escape agent.
Xu Wang - One of the best experts on this subject based on the ideXlab platform.
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detection of circulating tumor cells in human peripheral blood using surface enhanced raman scattering nanoparticles
Cancer Research, 2011Co-Authors: Xu Wang, Ximei Qian, Jonathan J Beitler, Zhuo Georgia Chen, Fadlo R Khuri, Melinda M Lewis, Hyung Ju C Shin, Shuming Nie, Dong M ShinAbstract:The detection and characterization of circulating tumor cells (CTCs) holds great promise for personalizing medicine and optimizing systemic therapy. However, low specificity, low sensitivity and the time consuming nature of current approaches have impeded clinical adoption. Here we report a new method using Surface-Enhanced Raman Spectroscopy (SERS) to directly measure targeted CTCs in the presence of white blood cells. SERS nanoparticles with epidermal growth factor (EGF) peptide as a Targeting Ligand have successfully identified CTCs in the peripheral blood of 19 patients with squamous cell carcinoma of the head and neck (SCCHN), with a range of 1–720 CTCs per milliliter of whole blood. Our technique may provide an important new clinical tool for management of patients with SCCHN and other cancers.
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detection of circulating tumor cells in human peripheral blood using surface enhanced raman scattering nanoparticles
Cancer Research, 2011Co-Authors: Xu Wang, Ximei Qian, Jonathan J Beitler, Zhuo Georgia Chen, Fadlo R Khuri, Melinda M Lewis, Hyung Ju C Shin, Dong M ShinAbstract:The detection and characterization of circulating tumor cells (CTCs) holds great promise for personalizing medicine and optimizing systemic therapy. However, low specificity, low sensitivity and the time consuming nature of current approaches have impeded clinical adoption. Here we report a new method using Surface-Enhanced Raman Spectroscopy (SERS) to directly measure targeted CTCs in the presence of white blood cells. SERS nanoparticles with epidermal growth factor (EGF) peptide as a Targeting Ligand have successfully identified CTCs in the peripheral blood of 19 patients with squamous cell carcinoma of the head and neck (SCCHN), with a range of 1–720 CTCs per milliliter of whole blood. Our technique may provide an important new clinical tool for management of patients with SCCHN and other cancers.
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detection of circulating tumor cells in human peripheral blood using surface enhanced raman scattering nanoparticles
Cancer Research, 2011Co-Authors: Xu Wang, Ximei Qian, Jonathan J Beitler, Zhuo Georgia Chen, Fadlo R Khuri, Melinda M Lewis, Hyung Ju C Shin, Shuming Nie, Dong M ShinAbstract:The detection and characterization of circulating tumor cells (CTC) holds great promise for personalizing medicine and optimizing systemic therapy. However, low specificity, low sensitivity, and the time consuming nature of current approaches have impeded clinical adoption. Here we report a new method using surface-enhanced Raman spectroscopy (SERS) to directly measure targeted CTCs in the presence of white blood cells. SERS nanoparticles with epidermal growth factor peptide as a Targeting Ligand have successfully identified CTCs in the peripheral blood of 19 patients with squamous cell carcinoma of the head and neck (SCCHN), with a range of 1 to 720 CTCs per milliliter of whole blood. Our technique may provide an important new clinical tool for management of patients with SCCHN and other cancers.
Yubin Huang - One of the best experts on this subject based on the ideXlab platform.
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tailoring platinum iv amphiphiles for self Targeting all in one assemblies as precise multimodal theranostic nanomedicine
ACS Nano, 2018Co-Authors: Qingfei Zhang, Xing-jie Liang, Xiaoyuan Chen, Haihua Xiao, Jianxun Ding, Xuesi Chen, Dongfang Zhou, Yubin HuangAbstract:Drug, Targeting Ligand, and imaging agent are the three essential components in a nanoparticle-based drug delivery system. However, tremendous batch-to-batch variation of composition and drug content typically accompany the current approaches of building these components together. Herein, we report the design of photoactivatable platinum(IV) (Pt(IV)) amphiphiles containing one or two hydrophilic lactose Targeting Ligands per hydrophobic Pt(IV) prodrug for an all-in-one precise nanomedicine. Self-assembly of these Pt(IV) amphiphiles results in either micelle or vesicle formation with a fixed Pt/Targeting moiety ratio and a constantly high content of Pt. The micelles and vesicles are capable of hepatoma cell-Targeting, fluorescence/Pt-based CT imaging and have shown effective anticancer efficacy under laser irradiation in vitro and in vivo. This photoactivatable, active self-Targeting, and multimodal theranostic amphiphile strategy shows great potential in constructing precise nanomedicine.
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Tailoring Platinum(IV) Amphiphiles for Self-Targeting All-in-One Assemblies as Precise Multimodal Theranostic Nanomedicine
2018Co-Authors: Qingfei Zhang, Xing-jie Liang, Xiaoyuan Chen, Haihua Xiao, Jianxun Ding, Xuesi Chen, Dongfang Zhou, Yubin HuangAbstract:Drug, Targeting Ligand, and imaging agent are the three essential components in a nanoparticle-based drug delivery system. However, tremendous batch-to-batch variation of composition and drug content typically accompany the current approaches of building these components together. Herein, we report the design of photoactivatable platinum(IV) (Pt(IV)) amphiphiles containing one or two hydrophilic lactose Targeting Ligands per hydrophobic Pt(IV) prodrug for an all-in-one precise nanomedicine. Self-assembly of these Pt(IV) amphiphiles results in either micelle or vesicle formation with a fixed Pt/Targeting moiety ratio and a constantly high content of Pt. The micelles and vesicles are capable of hepatoma cell-Targeting, fluorescence/Pt-based CT imaging and have shown effective anticancer efficacy under laser irradiation in vitro and in vivo. This photoactivatable, active self-Targeting, and multimodal theranostic amphiphile strategy shows great potential in constructing precise nanomedicine
