- Immunoproteasome Inhibitor-Doxorubicin Conjugates Target Multiple Myeloma Cells and Release Doxorubicin upon Low-Dose Photon Irradiation
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Proteasome inhibitors are established therapeutic agents for the treatment of hematological cancers, as are anthracyclines such as doxorubicin. We here present a new drug targeting approach that combines both drug classes into a single molecule. Doxorubicin was conjugated to an immunoproteasome-selective inhibitor via light-cleavable linkers, yielding peptide epoxyketone-doxorubicin prodrugs that remained selective and active toward immunoproteasomes. Upon cellular uptake and immunoproteasome inhibition, doxorubicin is released from the immunoproteasome inhibitor through photoirradiation. Multiple myeloma cells in this way take a double hit: immunoproteasome inhibition and doxorubicin-induced toxicity. Our strategy, which entails targeting of a cytotoxic agent, through a covalent enzyme inhibitor that is detrimental to tumor tissue in its own right, may find use in the search for improved anticancer drugs.
- Dekker, Patrick M.,Florea, Bogdan I.,Maiorana, Santina,Maurits, Elmer,Neefjes, Jacques J. C.,Overkleeft, Herman S.,Van De Graaff, Michel J.,Van Der Zanden, Sabina Y.,Van Kasteren, Sander I.,Wander, Dennis P. A.
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supporting information
p. 7250 - 7253
(2020/08/06)
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- Preparation method of disulfide bond-containing dual-response functional molecule and hydrogel microsphere and application thereof
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The invention discloses a disulfide bond-containing dual-response functional molecule, and the structural general formula of the disulfide bond-containing dual-response functional molecule is shown inthe specification. The invention also provides the dual
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Paragraph 0086-0088; 0100-0102
(2020/09/23)
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- Photoresponsive multifunctional chemical crosslinking agent and preparation method and application thereof
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The invention discloses a photoresponsive multifunctional chemical crosslinking agent. The structure of the crosslinking agent is shown in a formula I, wherein the definition of each substituent groupin the formula I is shown in the description. The prepa
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Paragraph 0120; 0129-0131
(2019/07/04)
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- Method for covalently immobilizing bioactive factor by material surface/interface photo-produced aldehyde/ketone group
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The invention relates to a method for immobilizing a bioactive factor by a material surface/interface photo-produced aldehyde/ketone group in a controllable mode. The method is characterized in that ato-be-immobilized bioactive factor does not need extra
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Paragraph 0082; 0115; 0116; 0194; 0197; 0198
(2018/11/22)
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- Photodegradable self-assembling PAMAM dendrons for gene delivery involving dendriplex formation and phototriggered circular DNA release
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For effective gene delivery, structural degradation of synthetic carriers is crucial to the release of nucleic acids on the transfection time scale. In this study, we have synthesized the amphiphilic dendritic scaffolds with a photolabile o-nitrobenzyl (o-NB) group that can enable the structural decomposition and controlled release of nucleic acids under active light stimulation. The amphiphilic counterpart composed of a lipophilic cholesterol and a hydrophilic poly(amido amine) (PAMAM) dendron allows the self-assembly into a core-shell-like pseudodendrimer above the critical aggregation concentration (CAC) of approximately 20 μM. On the basis of electrostatic interaction, the polycationic pseudodendrimers are capable of forming stable complexes with polyanionic cyclic reporter genes under low charge excess values, suggesting substantial binding affinity of the dendron assembly toward circular DNA. Because the o-NB group in the dendritic structure undergoes efficient photolytic cleavage, an in vitro test shows that thus-formed "dendriplexes" are readily dissociated under 365 nm light irradiation, causing effective dendron degradation accompanied by DNA release. This photochemical strategy provides an opportunity to control gene binding and release in a spatiotemporal manner.
- Lai, Yu-Sen,Kao, Chai-Lin,Chen, Ya-Pei,Fang, Chia-Chia,Hu, Chao-Chin,Chu, Chih-Chien
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supporting information
p. 2601 - 2608
(2016/03/22)
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- Micelle-to-vesicle morphological transition via light-induced rapid hydrophilic arm detachment from a star polymer
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Micelle-to-vesicle morphological transition has been achieved by light-induced rapid hydrophilic arm detachment from a star polymer. This provides a remote and clean method to control morphology transition of polymeric assemblies. The Royal Society of Che
- Du, Jin-Zhi,Long, Hong-Yan,Yuan, You-Yong,Song, Meng-Meng,Chen, Liang,Bi, Hong,Wang, Jun
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supporting information; experimental part
p. 1257 - 1259
(2012/03/09)
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- A diversity oriented synthesis of 3′-O-modified nucleoside triphosphates for DNA 'sequencing by synthesis'
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The nucleoside triphosphates 1, containing a photochemically cleavable group, and 2, having one that may be cleaved via palladium catalysis, were prepared as a prelude to investigating sequencing of DNA via sequencing by synthesis.
- Lu, Genliang,Burgess, Kevin
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p. 3902 - 3905
(2008/09/21)
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