Oligonucleotide-conjugated nanoparticles for targeted drug delivery via scavenger receptors class A: An in vitro assessment for proof-of-concept

Spherical nucleic acid gold nanoparticles represent a unique nanotechnology in which the spherical arrangement of oligonucleotides enables the nanoparticles to be efficiently internalized into cells expressing scavenger receptors class A (SR-A). Herein, we seek to replace the gold core with a biodegradable polymeric construct and explore their potential applications in targeted drug delivery. Oligonucleotide-conjugated poly(ethylene glycol)-block-poly(epsilon-caprolactone) was synthesized and characterized by H-1 NMR and gel electrophoresis. This polymer was applied to fabricate micellar nanoparticles (OLNNPs) by an anti-solvent method. These nanoparticles have a mean particle size about 58.1 nm with a narrow size distribution (PDI < 0.2) and they were also non-cytotoxic. Relative to non-targeted NPs, OLN-NPs exhibited substantially better uptake (3.94 x) in a mouse endothelial cell line (C166), attributing to lipid-raft-mediated endocytosis via SR-A. To explore the potential applications of OLN-NPs as drug carriers, paclitaxel, a poorly soluble anti-angiogenic compound, was selected as the model. OLN-NPs increased the solubility of paclitaxel by at least 300 x. The boosted drug solubility in conjunction with improved cellular uptake translated into enhanced in vitro efficacy in the inhibition of angiogenesis. In conclusions, OLN-NPs show considerable promise in targeted drug delivery and their potential applications should be further investigated.