Carbohydrate Systems in Targeted Drug Delivery: Expectation and Reality

Shchegravina, Ekaterina S.; Sachkova, A. A.; Usova, S. D.; Nyuchev, Alexander V.; Gracheva, Yu. A.; Fedorov, Alexey Yu.

doi:10.1134/s1068162021010222

Cited by 9 publications

(6 citation statements)

References 279 publications

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“…for the imaging of inflammation in the brain via sialyl LewisX-decorated MRI active nanoparticles 716 or galactosides as mono-or oligosaccharides for the targeting of galectins. 717 Using the above-mentioned advantages of glycomimetics over natural glycosides, this concept has also been implemented for the targeting of the selectins. (B) Computational modelling of the complex between 189 and human langerin was supported by NMR data and shows interaction of Lys313 with the sulfonamide linker and a T-stacking interaction between Phe315 and the tosyl group.…”

Section: Selectin-targetingmentioning

confidence: 99%

Glycomimetics for the inhibition and modulation of lectins

Leusmann,

Ménová,

Shanin

et al. 2023

Chem. Soc. Rev.

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Section: Selectin-targetingmentioning

confidence: 99%

Glycomimetics for the inhibition and modulation of lectins

Leusmann,

Ménová,

Shanin

et al. 2023

Chem. Soc. Rev.

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“…Solid carrier IV plus tyrosine can be used as a radioactive marker to evaluate the in vivo receptor-ligand interactions and GalNAc-siRNA conjugate uptake (Nair et al, 2014). Subsequently, the synthesized three-antenna GalNAc can combine with the 3′ end of the antisense chain of siRNA to form a GalNAc-siRNA conjugate (Shchegravina et al, 2021). siRNA can be synthesized directly by a chemical approach or by breaking long double-stranded RNA obtained by enzyme transcription into 21-23 nt siRNA under the action of the GalNAc-siRNA LNPs loaded siRNA (Aldosari et al, 2021;Zhang et al, 2021a;Lokugamage et al, 2021) Benefits & Challenges -can be injected subcutaneously, with only small chances of plasma siRNA degradation, rapid absorption, high uptake, and long half-life, (Springer and Dowdy, 2018)-endosomal escape, hepatotoxicity from off-target effects, acidic subcellular compartments, and extensive clearance, affect GalNAc efficiency and sequence barriers (Ayyar et al, 2021;Fairman et al, 2021;Fattal and Fay, 2021;Fumoto et al, 2021;Liu et al, 2021;Nanavati et al, 2021;Schlich et al, 2021) -avoid siRNA degradation of and the stimulation of the immune system by siRNA-lack efficient nuclear penetration and sustainable transgene expression (limitations such as poor biodistribution and possible toxic discharge), immunogenic and pose safety concerns of liposome molecules and limited efficacy and biosafety since unconjugated liposomes cannot achieve targeted delivery (Ickenstein and Garidel, 2019;Hu et al, 2020;Blakney et al, 2021;Hassett et al, 2021;Maestro et al, 2021) Composition Specific arrangement of nucleoside, pO/PS linkage and monovalent GalNAc (Matsuda et al, 2015) polyethylene glycol-lipid conjugates (PEG-DMG), ionizable amino lipids (DLin-MC3-DMA), distearyl phosphatidylcholine (DSPC) and cholesterol…”

Section: Structure and Mechanism Of Actionmentioning

confidence: 99%

Section: Galnac-sirna Conjugatesmentioning

confidence: 99%

“…siRNA can be synthesized directly by a chemical approach or by breaking long double-stranded RNA obtained by enzyme transcription into 21–23 nt siRNA under the action of the cytoplasmic RNase III endonuclease Dicer, which has two protruding nucleotides at the 3′ hydroxyl end, a phosphate terminal at the 5′ end and a complementary double-stranded region of 19 nt in the middle ( Adachi et al, 2021 ; Paro et al, 2021 ). When GalNAc-siRNA is introduced into the body and binds to ASGPR on the surface of hepatocytes, the siRNA GalNAc-ASGPR complex is separated in the endosome ( Holland et al, 2021 ; Shchegravina et al, 2021 ). Thereafter, siRNA escapes from the endosome, and GalNAc is degraded and excreted out of the endosome.…”

Section: Galnac-sirna Conjugatesmentioning

confidence: 99%

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The therapeutic prospects of N-acetylgalactosamine-siRNA conjugates

Zhang

Liang²,

Liang³

et al. 2022

Front. Pharmacol.

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RNA interference has become increasingly used for genetic therapy following the rapid development of oligonucleotide drugs. Significant progress has been made in its delivery system and implementation in the treatment of target organs. After a brief introduction of RNA interference technology and siRNA, the efficiency and stability of GalNAc-siRNA conjugates are highlighted since several oligonucleotide drugs of GalNAc have been approved for clinical use in recent years. The structure and features of GalNAc-siRNA conjugates are studied and the clinical efficiency and limitations of oligonucleotide-based drugs are summarized and investigated. Furthermore, another delivery system, lipid nanoparticles, that confer many advantages, is concluded, includ-ing stability and mass production, compared with GalNAc-siRNA conjugates. Importantly, developing new approaches for the use of oligonucleotide drugs brings hope to genetic therapy.

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“…The hepatocyte plasma membranes contain C-type lectin receptors (asialoglycoprotein receptors), which selectively bind unprotected galactose or N -acetylgalactosamine residues in glycoproteins. The conjugates then enter the endosome via a clathrin-dependent mechanism [ 12 ].…”

Section: Properties and Main Functions Of Sialic Acidsmentioning

confidence: 99%

Clinical and Diagnostic Significance of Sialic Acids Determination in Biological Material

Vol'khina

Butolin

2022

Biochem. Moscow Suppl. Ser. B

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Sialic acids (SA) are neuraminic acid derivatives, located at the terminal position in the chains of monosaccharide residues of various glycoconjugates. SA play a dual role: they either mask recognition sites, or, on the contrary, represent biological targets that can be recognized by receptor proteins and serve as ligands. The desialylation/sialylation processes can be considered as a dynamic modification regulated by sialyltransferases and sialidases in response to external or internal stimuli. This review describes the structural and functional diversity and the potential use of SA fractions as biomarkers for various pathological conditions. Almost any extreme impact on the body and inflammatory processes are accompanied by an increase in the level of both total and free SA in the blood and tissues. Possible reasons for the increase of sialoglycoconjugate metabolism indicators in biological material include: (i) activation of the hepatocyte synthesis and secretion of various acute-phase proteins, many of which are sialoglycoproteins, (ii) impaired membrane integrity and destruction of body cells, (iii) high activity of sialidases (neurominidases) and sialyltransferases. Most acute and chronic liver diseases are characterized by the decrease in the total level of SA in the blood serum (because many plasma proteins are synthesized and glycosylated in hepatocytes). Aberrant sialylation results in changes of sialoglycoconjugate structure, its ability to perform biological functions and sialoglycoconjugate half-life. Glycosylation is the most common post-translational modification of proteins in the virus, which not only promotes the formation of specific conformation of viral proteins, but also modulates their interaction with receptors and affects host cell recognition, viral replication and infectivity. Serum total SA concentration increases in some benign and inflammatory conditions, which indicates a lack of specificity and limits their use for early detection and screening of neoplastic diseases. Clinical and diagnostic value of determining the sialoglycoconjugate metabolic indicators, including changes in the content of both SA fractions and specific proteins in various biological fluids and tissues, consists in establishing the causes and mechanisms of biochemical changes in the body in certain diseases. In combination with the measurement of existing markers, they can be used to improve diagnosis, staging and monitoring of therapeutic response in some pathological conditions where the need for specificity is less than for specific diagnostics.

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Carbohydrate Systems in Targeted Drug Delivery: Expectation and Reality

Cited by 9 publications

References 279 publications

Glycomimetics for the inhibition and modulation of lectins

Glycomimetics for the inhibition and modulation of lectins

The therapeutic prospects of N-acetylgalactosamine-siRNA conjugates

Clinical and Diagnostic Significance of Sialic Acids Determination in Biological Material

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