A New DNA-Based Carrier for Targeting and Intracellular Transport of Therapeutics

S. Muro
University of Maryland College Park, US

Keywords: DNA structures, dendrimer, drug targeting, endocytosis

Summary:

Nano-scale drug delivery systems can improve drug solubility, circulation, targeting, and release. Many types of drug carriers have been reported, which vary broadly in terms of chemistry, architecture, and functionalization. However, only a few designs are amenable for clinical use. A key factor determining translation of drug delivery systems is biocompatibility, where carriers based on natural biological macromolecules hold considerable promise. For the first time, we show proof-of-concept for the use of a new nanocarrier composed of DNA, a natural material, assembled as a 150 nm dendrimer (nucleodendrimer). Nucleodendrimers were coupled to antibodies against intercellular adhesion molecule 1 (ICAM-1), a marker expressed on cells altered by many pathological conditions. As for anti-ICAM polymer (polysrytene and PLGA) nanoparticles previously characterized, ICAM-1-targeted nucleodendrimers bound specifically to ICAM-1-expressing endothelial cells and also organs (e.g., lungs) after i.v. injection in mice. ICAM-1-targeted nucleodendrimers entered cells and showed punctate distribution at 37°C, but not at 4ºC, indicating endocytosis similar to anti-ICAM polymer nanoparticles. Nucleodendrimer targeting was also proven for other receptors (transferrin receptor and mannose-6-phosphate receptor) and cell types (fibroblasts, mesothelioma cells). Hence, nucleodendrimers represent a new type of carrier for drug targeting and intracellular transport.