Screening of different expression miRNAs in pulmonary injury induced by nanosized SiO2

Abstract

Cationic dendrimers arewidely used as non-viral vectors for the delivery of DNA and siRNA, however, their applications in gene therapy are limited due to moderate transfection efficacy and serious toxicity. As a result, dendrimers are usually modified with lipids, fluorous compounds, amino acids, cyclodextrins, cationic moieties, polymers, peptides, proteins, and nanoparticles to improve their transfection efficacy and biocompatibility. Up to now, the structure–function relationships of these surface-modified dendrimers in gene delivery are poorly understood. Here, we prepared a library of surface-engineered dendrimers (~270 compounds), which is used as a screening pool to discover efficient siRNA vectors. HeLa, MDAMB-231 andA549 cells stably expressing luciferase genewere used asmodel cells. The modified ligands on dendrimers include amino acids, lipids and fluorous compounds, aromatic compounds, and heterocyclic compounds. Preliminary results show that eight surface-engineered dendrimers have efficient siRNA delivery efficacy (N66.6% gene silencing efficacy) on the model cells (Figure 1). Their efficacies are superior to several commercial transfection reagents such as Lipofectamine 2000. The structure–function relationships of thesematerials are revealed. The result will play an important role in the design of efficient and low cytotoxic polymeric vectors for siRNA delivery.