Glycotargeting to improve cellular delivery efficiency of nucleic acids

Abstract

Nucleic acids bearing glycans of various structures have been under vigorous investigation in the past decade. The carbohydrate moieties of such complexes can serve as recognition sites for carbohydrate-binding proteins-lectins-and initiate receptor-mediated endocytosis. Therefore, carbohydrates can enhance cell targeting and internalization of nucleic acids that are associated with them and thus improve the bioavailability of nucleic acids as therapeutic agents. This review summarizes nucleic acid glycosylation in nature and approaches for the preparation of both non-covalently associated and covalently-linked carbohydrate-nucleic acid complexes.

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

“…Antibodies (their size is about 12 nm) endowed with fluorescent dyes (e.g., Alexa Fluor 488 λEm=525 nm and Texas Red λEm=609 nm) [15][16][17] were used in the development of a wide range of effective targeted therapies [18][19][20][21][22] but they create clustering artifacts due to limited antibody penetration, which have an impact on insufficient labeling density. Thus, ligands that have been exploited for chemotherapeutic agent targeting systems can include monoclonal antibodies [23][24][25][26][27][28] but also low molecular weight receptor-binding conjugates such as dyelabeled peptides (arginine-glycine-aspartic acid-Cyt5,5) [29], peptide hormones [30,31], receptor antagonist and agonists [32], aptamers [33][34][35], transferrin [36][37], oligosaccharides [38], glycoconiugates [39], polyunsaturated fatty acids [40], oligopeptides [41,42], vitamin B12 [43], folic acid [44][45][46][47][48][49][50][51][52][53][54] and hyaluronic acid [55,56]. These ligands can be regarded as a tumor-specific receptor to construct a "guided molecular ...…”

Design of siRNA Therapeutics from the Molecular Scale

“…While easily applied for complexes with encapsulated siRNA, complexes with surface attached siRNA will have reduced surface area for siRNA attachment with the addition of each ligand. Active targeting has proven effective in HCC models [235,236,237], but the strategies for functionalizing delivery vehicles with ligands are not well defined. In situations where targeting cannot be improved through molecular approaches, magnetic nanoparticles can be directed to a specific target region via external magnetic fields, though this can be logistically difficult [200].…”

Synthesis and Cellular Uptake of Fluorescently Labeled Multivalent Hyaluronan Disaccharide Conjugates of Oligonucleotide Phosphorothioates

“…Purification by silica gel chromatography (7% i-PrOH in CH 2 Cl 2 ) gave 12 as white solid in 90% yield (1.60 g). 1 (13). Compound 12 (520 mg, 0.820 mmol) was dissolved in wet MeCN (5 mL, 0.8 v % water) and cooled to 0°C.…”

“…Attempts to perform the oxidation directly in wet dichloromethane failed. Finally, the primary hydroxyl function of 12 was oxidized to a carboxyl group (13) with periodic acid in the presence of a catalytic amount of chromium trioxide in wet acetonitrile (53). The anomeric aldehyde tether was generated by osmium tetroxide catalyzed periodate oxidation (54,55), which gave the protected hyaluronan disaccharide 1.…”