178685-33-1Relevant academic research and scientific papers
Targeted Delivery of a Mannose-Conjugated BODIPY Photosensitizer by Nanomicelles for Photodynamic Breast Cancer Therapy
Zhang, Quan,Cai, Ying,Li, Qiu-Yan,Hao, Lin-Na,Ma, Zheng,Wang, Xiao-Jun,Yin, Jian
, p. 14307 - 14315 (2017)
The targeted delivery of a photosensitizer (PS) with appropriate carriers represents an attractive means of selectively delivering cargo to target tissues or subcellular compartments for photodynamic therapy (PDT). Herein, a three-arm distyryl BODIPY derivative conjugated with mannose units (denoted by BTM) that can co-assemble with Tween 80 to form nanomicelles (BTM-NMs) for targeted PDT is reported. MDA-MB-231 breast cancer cells recognized and specifically internalized BTM-NMs via mannose-receptor-mediated endocytosis with preferential accumulation in the lysosomes. These NMs could disassemble in cell lysosomes and subsequently induce highly efficient singlet oxygen (1O2) generation upon light irradiation. 1O2 disrupted the lysosomal membrane and promoted the escape of BTM from the lysosome into the cytoplasm, thereby resulting in the efficient and selective killing of cancer cells through PDT. This study may provide a new strategy for designing targeted PDT systems to fight cancer.
Radioiodinated estradiol dimer for estrogen receptor targeted breast cancer imaging
Xu, Duo,Peng, Chenyu,Gao, Fei,Guo, Zhide,Zhuang, Rongqiang,Su, Xinhui,Zhang, Xianzhong
, p. 1332 - 1340 (2020)
The aim of this study was to develop a 1-(2-(2-(2-(1,2,3-triazol)ethoxy)ethoxy)ethyl)-5-[125/131I]iodo-1,2,3-triazole-diestradiol ([125/131I]ITE2), for estrogen receptor (ER)-expressing breast cancer imaging with single-photon emission computed tomography (SPECT). [125/131I]ITE2 was prepared in good radiochemical yield (94.4?±?0.4%) with high radiochemical purity (>99%). [125/131I]ITE2 had good stability in vitro and moderate molar activity (0.3?±?0.2?GBq/μmol). Higher uptake in ER-positive MCF-7 cells than that of ER-negative MDA-MB-231 cells was observed at all time points. Rats biodistribution showed that [131I]ITE2 had high uptake in ER-abundant uterine and ovarian (5.7?±?0.4 and 10.1?±?1.4%ID/g at 1?hr postinjection) and could be blocked by co-injection of estradiol (2.7?±?0.1 and 5.5?±?0.4%ID/g) obviously. In the SPECT/CT imaging study, [125I]ITE2 showed significant higher uptake in MCF-7 tumor (3.1?±?0.4%ID/g) than that of MDA-MB-231 (0.9?±?0.1%ID/g). Furthermore, the specific uptake of [125I]ITE2 in ER-positive MCF-7 tumor could be blocked effectively by preadministration of fulvestrant (1.2?±?0.4%ID/g). A novel radioiodinated dimeric estrogen was designed and synthesized with promising ER targeting ability and specificity. It is worthy of further investigation to validate the advantages of the dimer in ER-positive breast cancer diagnosis.
Novel unit B cryptophycin analogues as payloads for targeted therapy
Figueras, Eduard,Borbély, Adina,Ismail, Mohamed,Frese, Marcel,Sewald, Norbert
, p. 1281 - 1286 (2018)
Cryptophycins are naturally occurring cytotoxins with great potential for chemotherapy. Since targeted therapy provides new perspectives for treatment of cancer, new potent analogues of cytotoxic agents containing functional groups for conjugation to homing devices are required. We describe the design, synthesis and biological evaluation of three new unit B cryptophycin analogues. The O-methyl group of the unit B D-tyrosine analogue was replaced by an O-(allyloxyethyl) moiety, an O-(hydroxyethyl) group, or an O-(((azidoethoxy)ethoxy)ethoyxethyl) substituent. While the former two maintain cytotoxicity in the subnanomolar range, the attachment of the triethylene glycol spacer with a terminal azide results in a complete loss of activity. Docking studies of the novel cryptophycin analogues to β-tubulin provided a rationale for the observed cytotoxicities.
Dendrimer-Based Signal Amplification of Click-Labelled DNA in Situ
Raddaoui, Nada,Stazzoni, Samuele,M?ckl, Leonhard,Viverge, Bastien,Geiger, Florian,Engelke, Hanna,Br?uchle, Christoph,Carell, Thomas
, p. 1716 - 1720 (2017)
The in vivo incorporation of alkyne-modified bases into the genome of cells is today the basis for the efficient detection of cell proliferation. Cells are grown in the presence of ethinyl-dU (EdU), fixed and permeabilised. The incorporated alkynes are then efficiently detected by using azide-containing fluorophores and the CuI-catalysed alkyne–azide click reaction. For a world in which constant improvement in the sensitivity of a given method is driving diagnostic advancement, we developed azide- and alkyne-modified dendrimers that allow the establishment of sandwich-type detection assays that show significantly improved signal intensities and signal-to-noise ratios far beyond that which is currently possible.
Synthesis and preliminary evaluation of a 18F-labeled ethisterone derivative [18F]EAEF for progesterone receptor targeting
Wu, Xiaowei,You, Linyi,Zhang, Deliang,Gao, Mengna,Li, Zijing,Xu, Duo,Zhang, Pu,Huang, Lumei,Zhuang, Rongqiang,Wu, Hua,Zhang, Xianzhong
, p. 559 - 565 (2017)
To develop a novel progesterone receptor-targeting probe for positron emission tomography imaging, an ethisterone derivative [18F]EAEF was designed and prepared in high decay-corrected radiochemical yield (30–35%) with good radiochemical purity (>98%). [18F]EAEF is a lipophilic tracer (logP?=?0.53?±?0.06) with very good stability in saline and serum. In the biodistribution study, high radioactivity accumulation of [18F]EAEF were found in uterus (5.73?±?1.83% ID/g) and ovary (4.05?±?0.73% ID/g) at 2?hr postinjection (p.i.), which have high progesterone receptor expression after treated with estradiol, while the muscle background has very low uptake (0.50?±?0.17% ID/g). For positron emission tomography imaging, [18F]EAEF showed high uptake in progesterone receptor-positive MCF-7 tumor (3.15?±?0.07% ID/g at 2?hr p.i.) with good tumor to muscle ratio (2.90), and obvious lower tumor uptakes were observed in MCF-7 with EAEF blocking (1.84?±?0.05% ID/g at 2?hr p.i.) or in progesterone receptor-negative MDA-MB-231 tumor (1.80?±?0.03% ID/g at 2?hr p.i.). Based on the good stability and specificity of [18F]EAEF, it may be a good candidate for imaging progesterone receptor and worth further investigation.
Enzyme-responsive snap-top covered silica nanocontainers
Patel, Kaushik,Angelos, Sarah,Dichtel, William R.,Coskun, Ali,Yang, Ying-Wei,Zink, Jeffrey I.,Stoddart, J. Fraser
, p. 2382 - 2383 (2008)
Mesoporous silica nanoparticles, capable of storing a payload of small molecules and releasing it following specific catalytic activation by an esterase, have been designed and fabricated. The storage and release of the payload is controlled by the presence of [2]rotaxanes, which consist of tri(ethylene glycol) chains threaded by α-cyclodextrin tori, located on the surfaces of the nanoparticles and terminated by a large stoppering group. These modified silica nanoparticles are capable of encapsulating guest molecules when the [2]rotaxanes are present. The bulky stoppers, which serve to hold the tori in place, are stable under physiological conditions but are cleaved by the catalytic action of an enzyme, causing dethreading of the tori and release of the guest molecules from the pores of the nanoparticles. These snap-top covered silica nanocontainers (SCSNs) are prepared by a modular synthetic method, in which the stoppering unit, incorporated in the final step of the synthesis, may be changed at will to target the response of the system to any of a number of hydrolytic enzymes. Here, the design, synthesis, and operation of model SCSNs that open in the presence of porcine liver esterase (PLE) are reported. The empty pores of the silica nanoparticles were loaded with luminescent dye molecules (rhodamine B), and stoppering units that incorporate adamantyl ester moieties were then attached in the presence of α-cyclodextrin using the copper-catalyzed azide-alkyne cycloaddition (CuAAC), closing the SCSNs. The release of rhodamine-B from the pores of theSCSN, following PLE-mediated hydrolysis of the stoppers, was monitored using fluorescence spectroscopy. Copyright
Carbonic Anhydrase Inhibitors Featuring a Porphyrin Scaffold: Synthesis, Optical and Biological Properties
Clément, Sébastien,Gary-Bobo, Magali,Gerbier, Philippe,Merabti, Amina,Nguyen, Christophe,Nocentini, Alessio,Richeter, Sébastien,Roger, Maxime,Supuran, Claudiu T.,Winum, Jean-Yves
, (2022/02/19)
The synthesis, characterization and study of optical properties of innovative tetrafunctionalized zinc(II) porphyrins with carbonic anhydrase (CA) inhibitors in sulfonamide and coumarin series are described. The synthetic methodology relies on the prepara
CELL SURFACE RECEPTOR BINDING COMPOUNDS AND CONJUGATES
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Paragraph 001166-001168, (2021/07/17)
The present disclosure provides a class of compounds including a ligand moiety that specifically binds to a cell surface receptor, such as a mannose-6-phosphate receptor (M6PR) or a cell surface asialoglycoprotein receptor (ASGPR). The cell surface M6PR or ASGPR binding compounds can trigger the receptor to internalize into the cell a bound compound. The ligand moieties of this disclosure can be linked to a variety of moieties of interest without impacting the specific binding to, and function of, the cell surface receptor, e.g., M6PR or ASGPR. Also provided are compounds that are conjugates of the ligand moieties linked to a biomolecule, such as an antibody, which conjugates can harness cellular pathways to remove specific proteins of interest from the cell surface or from the extracellular milieu. Also provided are methods of using the conjugates to target a polypeptide of interest for sequestration and/or lysosomal degradation.
Compound for inducing Tau protein degradation based on CRBN ligand as well as preparation method, pharmaceutical composition and application of compound
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Paragraph 0058-0060, (2021/08/28)
The invention discloses a compound for inducing Tau protein degradation based on a CRBN ligand. The compound is a compound as shown in a formula (I) or pharmaceutically acceptable salt and hydrate of the compound. Wherein n is an integer from 1 to 10. The invention also discloses a preparation method of the compound, a pharmaceutical composition and application of the compound in preparation of drugs for preventing or/and treating neurodegenerative diseases. The compound disclosed by the invention can be used for reducing the dosage of a medicine and relieving toxic and side effects by virtue of a unique protein degradation inducing mechanism.
An Activatable Near-Infrared Fluorescence Probe for in Vivo Imaging of Acute Kidney Injury by Targeting Phosphatidylserine and Caspase-3
Wang, Yuqi,Weng, Jianhui,Ye, Deju,Zhang, Yan
, p. 18294 - 18304 (2021/11/10)
Renal-clearable and target-responsive near-infrared (NIR) fluorescent imaging probes have been promising for in vivo diagnosis of acute kidney injury (AKI). However, designing an imaging probe that is renal-clearable and concurrently responsive toward mul
