Hepatic-Targeted Gene Delivery Using Cationic Mannan Vehicle

Abstract

The incidence of hepatic diseases continuously increases worldwide and causes significant mortality because of inefficient pharmacotherapy. Gene therapy is a new strategy in the treatment of hepatic diseases, but the disadvantages of insufficient retention in the liver and undesirable side effects hinder its application. In this study, we developed a novel nonviral vehicle targeted to liver. Mannan was cationized with spermine at varying grafted ratios to deliver the gene and was optimized in cytotoxicity and transfection in vitro. A spermine-mannan (SM)-based delivery system was proven to be hepatic targeted and was capable of prolonging the gene retention period in the liver. Moreover, SM at N/P of 20 was confirmed to be less interfered with by the serum. Optimized SM vehicle has relatively high hepatic transfection with almost no toxicity induction in the liver, which highlighted its potential in the treatment of hepatic diseases.

18F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography

“…To conjugate [ 18 F]­BCN or [ 19 F]­BCN to mannan, the molecular structure of mannan needs to be functionalized with tetrazine moieties. In literature, strategies for activation of mannan include periodate oxidation, cyanylation and carbamoylation. − In periodate oxidation reactions, part of the hexasaccharide rings is opened to form aldehydes, and new epitopes may be generated in the resulted conjugates . Cyanylation or carbamoylation activate some of the hydroxyl groups without breaking the sugar ring structures.…”

Carbohydrate-Based Materials for Targeted Delivery of Drugs and Genes to the Liver

“…Mannose was activated by N,N′-Dicyclohexylcarbodiimide followed by their conjugation with spermine. However, in vivo evaluation of complexes revealed that cationic character of conjugates overshadowed the targeting efficacies of glycans [64].…”