- Disulfide bond based cascade reduction-responsive Pt(IV) nanoassemblies for improved anti-tumor efficiency and biosafety
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The platinum-based drugs prevail in the therapy of malignant tumors treatment. However, their clinical outcomes have been heavily restricted by severe systemic toxicities. To ensure biosafety and efficiency, herein, we constructed a disulfide bond inserted Pt(IV) self-assembled nanoplatform that is selectively activated by rich glutathione (GSH) in tumor site. Disulfide bond was introduced into the conjugates of oxaliplatin (IV) and oleic acid (OA) which conferred cascade reduction-responsiveness to nanoassemblies. Disulfide bond cleavage and reduction of Pt(IV) center occur sequentially as a cascade process. In comparison to oxaliplatin solution, Pt(IV) nanoparticles (NPs) achieved prolonged blood circulation and higher maximum tolerated doses. Furthermore, Oxa(IV)-SS-OA prodrug NPs exhibited potent anti-tumor efficiency against 4T1 cells and low toxicities in other normal tissues, which offers a promising nano-platform for potential clinical application.
- Kuang, Xiao,Chi, Dongxu,Li, Jinbo,Guo, Chunlin,Yang, Yinxian,Zhou, Shuang,Luo, Cong,Liu, Hongzhuo,He, Zhonggui,Wang, Yongjun
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- Disulfide bond bridged docetaxel-fatty acid prodrugs and self-assembled nanoparticles thereof
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According to the invention, a series of reduction-sensitive disulfide bond bridged docetaxel fatty acid prodrugs are designed and synthesized. The series of prodrugs can be self-assembled into a nano drug delivery system through a one-step nano precipitation method. The nano drug delivery system has the following advantages that: docetaxel is prepared into a disulfide bond connected prodrug, so that the system toxicity of a docetaxel parent drug is reduced, the parent drug can be specifically released in a high reduction environment in tumor cells, and the effects of synergy and toxicity reduction are achieved; the drug loading capacity is high, the use of a solubilizer with higher toxicity is avoided, and the tolerance and the compliance of a patient are expected to be improved; through the one-step nano precipitation method, the preparation process is simple, and large-scale production is easy; the nanoparticles are small and uniform in particle size and are easily enriched at a tumor part through an EPR effect; and surface modification is easy, and removal of a reticuloendothelial system can be slowed down through modification of PEG modification.
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Paragraph 0034-0035
(2021/04/07)
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- GEMCITABINE AMPHIPHILE PRODRUGS
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The present invention relates to improved prodrugs, and compositions thereof. In particular, it relates to amphiphilic gemcitabine prodrugs or amphiphilic prodrugs of other biologically active molecules with the capacity to make liquid crystalline nanostructured nanoparticles, and uses thereof to treat animals, including humans.
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Page/Page column 54
(2019/11/12)
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- Docetaxel prodrug self-assembled nanosystem: Synthesis, formulation and cytotoxicity
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Conventional drug delivery systems of docetaxel (DTX) are challenged with low drug loading efficiency and potential carriers-induced toxicity. In this work, a docetaxel prodrug self-assembled nanosystem was designed and synthesized by conjugating docetaxel with oleic acid (OA) exploring a thioether as the linker, which is redox-sensitive to the redox environment within tumor cells. Notably, the carrier-free nanomedicine which does not need any carrier has obviously high drug loading that reaches 58%. Moreover, the cytotoxicity of DTX-S-OA maintains an equal level with DTX. The novel prodrug conjugate therefore has a promising perspective as carrier-free nanomedicine for cancer therapy due to its high drug loading property, redox-sensitive release and long circulation mechanism.
- Jing, Fanbo,Guo, Qie,Xu, Wen,Qu, Haijun,Sui, Zhongguo
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supporting information
p. 826 - 830
(2018/02/06)
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- LIPIDS AND COMPLEXES FOR THE DELIVERY OF BIOLOGICALLY-ACTIVE MATERIAL TO CELLS
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A lipid comprising a tri-chain cation of formula (la) having a cationic head group and three C12-24 hydrocarbyl groups for use in non-viral gene delivery systems, for example in the formation of lipopolyplex transfection vectors. Exceptionally good nucleic acid transfection is observed when nucleic acid and targeting peptides are formulated with the lipid of the invention (or lipid formulated with a co-lipid) into a LPD complex.
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Page/Page column 30; 31
(2017/09/27)
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- PRECIPITATION POLYMERIZATION IN THE PRESENCE OF GLYCERIN MONOSTEARATE
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A process for preparing a copolymer composition A) by free-radical copolymerization of a monomer composition comprising: a) acrylic acid, b) optionally at least one compound, different from a), having a free-radically polymerizable, α,β-ethylenically unsaturated double bond and at least one anionogenic and/or anionic group per molecule, c) at least one free-radically polymerizable crosslinking compound which comprises at least two α,β-ethylenically unsaturated double bonds per molecule. The process is performed by precipitation polymerization in the presence of an auxiliary composition H) comprising H1) glycerol monostearate, and H2) at least one compound with an HLB value in the range from 4 to 10, selected from water-insoluble natural waxes, nonionic emulsifiers and mixtures thereof.
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- Structure/activity relationships in lysophosphatidic acid: The 2- hydroxyl moiety
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Although lipid phosphoric acid mediators such as lysophosphatidic acid (LPA) are now recognized widely as intercellular signaling molecules, the medicinal chemistry of these mediators is poorly developed. With the goal of achieving a better understanding of the structure activity relationships in LPA, we have synthesized and tested a series of LPA analogs that lack the 2- hydroxyl moiety. Our series consisted of compounds with 2, 3, or 4 carbon diol or amino alcohol backbones and oleoyl or palmitoleoyl acyl groups. These molecules cannot be acylated further to form phosphatidic acids, nor do they have chiral centers. The rank order potency of these compounds in mobilization of calcium in MDA MB-231 cells suggested a maximum optimal chain length of 24-25 atoms. However, high potency for the inhibition of adenylyl cyclase in these cells was achieved only by one compound that also contained a dissociable proton five bond lengths from the phosphorus atom. That compound, N-oleoyl-2-hydroxyethyl-1-phosphate, was nearly equipotent to 1- oleoyl LPA in both assays. The striking mimicry of LPA by the ethanolamine- based compound and the presence of fatty acid amides in tissue prompts us to propose that phosphorylated N-acyl ethanolamides occur naturally.
- Lynch, Kevin R.,Hopper, Darrin W.,Carlisle, Steven J.,Catalano, John G.,Zhang, Ming,Macdonald, Timothy L.
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- Facile synthesis of lysophospholipids containing unsaturated fatty acid chains
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The efficient synthesis of polyunsaturated phospholipids is challenging due to the sensitivity of the unsaturated moiety to the conditions employed in phosphate ester deprotection. We discuss here three independent methods that resolve this issue and enable the synthesis of a series of unsaturated lysophosphatidic acid mimics for the development of a more comprehensive understanding of the structure-activity relationship in this series.
- Hopper, Darrin W.,Catalano, John G.,Macdonald, Timothy L.
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p. 7871 - 7874
(2007/10/03)
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