19374-87-9Relevant articles and documents
Intracellularly Actuated Quantum Dot-Peptide-Doxorubicin Nanobioconjugates for Controlled Drug Delivery via the Endocytic Pathway
Sangtani, Ajmeeta,Petryayeva, Eleonora,Wu, Miao,Susumu, Kimihiro,Oh, Eunkeu,Huston, Alan L.,Lasarte-Aragones, Guillermo,Medintz, Igor L.,Algar, W. Russ,Delehanty, James B.
, p. 136 - 148 (2018)
Nanoparticle (NP)-mediated drug delivery (NMDD) has emerged as a novel method to overcome the limitations of traditional systemic delivery of therapeutics, including the controlled release of the NP-associated drug cargo. Currently, our most advanced understanding of how to control NP-associated cargos is in the context of soft nanoparticles (e.g., liposomes), but less is known about controlling the release of cargos from the surface of hard NPs (e.g., gold NPs). Here we employ a semiconductor quantum dot (QD) as a prototypical hard NP platform and use intracellularly triggered actuation to achieve spatiotemporal control of drug release and modulation of drug efficacy. Conjugated to the QD are two peptides: (1) a cell-penetrating peptide (CPP) that facilitates uptake of the conjugate into the endocytic pathway and (2) a display peptide conjugated to doxorubicin (DOX) via three different linkages (ester, disulfide, and hydrazone) that are responsive to enzymatic cleavage, reducing conditions, and low pH, respectively. Formation of the QD-[peptide-DOX]-CPP complex is driven by self-assembly that allows control over both the ratio of each peptide species conjugated to the QD and the eventual drug dose delivered to cells. F?rster resonance energy transfer assays confirmed successful assembly of the QD-peptide complexes and functionality of the linkages. Confocal microscopy was employed to visualize residence of the QD-[peptide-DOX]-CPP complexes in the endocytic pathway, and distinct differences in DOX localization were noted for the ester linkage, which showed clear signs of nuclear delivery versus the hydrazone, disulfide, and amide control. Finally, delivery of the QD-[peptide-DOX]-CPP conjugate resulted in cytotoxicity for the ester linkage that was comparable to free DOX. Attachment of DOX via the hydrazone linkage facilitated intermediary toxicity, while the disulfide and amide control linkages showed minimal toxicity. Our data demonstrate the utility of hard NP-peptide bioconjugates to function as multifunctional scaffolds for simultaneous control over cellular drug uptake and toxicity and the vital role played by the nature of the chemical linkage that appends the drug to the NP carrier.
Enzymatic synthesis of trideuterated sialosides
Cai, Zhi-P.,Conway, Louis P.,Huang, Ying Y.,Wang, Wen J.,Laborda, Pedro,Wang, Ting,Lu, Ai M.,Yao, Hong L.,Huang, Kun,Flitsch, Sabine L.,Liu, Li,Voglmeir, Josef
, (2019/04/17)
Sialic acids are a family of acidic monosaccharides often found on the termini of cell surface proteins or lipid glycoconjugates of higher animals. Herein we describe the enzymatic synthesis of the two isotopically labeled sialic acid derivatives d3-X-Gal-a-2,3-Neu5Ac and d3-X-Gal-a-2,3-Neu5Gc. Using deuterium oxide as the reaction solvent, deuterium atoms could be successfully introduced during the enzymatic epimerization and aldol addition reactions when the sialosides were generated. NMR and mass spectrometric analyses confirmed that the resulting sialosides were indeed tri-deuterated. These compounds may be of interest as internal standards in liquid chromatography/mass spectrometric assays for biochemical or clinical studies of sialic acids. This was further exemplified by the use of this tri-deuterated sialosides as internal standards for the quantification of sialic acids in meat and egg samples.
Design and synthesis of active heparan sulfate-based probes
Zhou, Wen,Hsieh, Po-Hung,Xu, Yongmei,O'Leary, Timothy R.,Huang, Xuefei,Liu, Jian
supporting information, p. 11019 - 11021 (2015/07/02)
A chemoenzymatic approach for synthesizing heparan sulfate oligosaccharides with a reactive diazoacetyl saccharide residue is reported. The resultant oligosaccharides were demonstrated to serve as specific inhibitors for heparan sulfate sulfotransferases,
