Influence of nanoparticle shapes on cellular uptake of paclitaxel loaded nanoparticles in 2D and 3D cancer models

Abstract

Enhanced cellular uptake and efficient penetration of nanocarriers inside tumors is paramount to successful anti-cancer therapy. While many studies have shown the important role nanoparticle shape plays in cellular uptake, no detailed conclusions on the most efficient drug carrier shape have been drawn at this stage. Here, a series of fructose-based amphiphilic block copolymers poly(1-O-MAFru)-b-PMMA are synthesized via RAFT polymerization. Three different morphologies (spheres, rods and vesicles) are prepared by self-assembly under different processing conditions. The shape effects of fructose-coated nanoparticles on cellular uptake by two breast cancer cell lines (MCF-7 cells and MDA-MB-231 cells) in 2D and 3D cell culture models are investigated. The cytotoxicity of corresponding paclitaxel-loaded nanoparticles are tested as well to give a comprehensive comparison between cellular uptake and resulting therapeutic efficacy after drug encapsulation in both cell culture models. Consistent results in 2D models confirm the shape effect of nanoparticles on cellular uptake. Unexpectedly, the shape does influence significantly the cell growth inhibition in 3D multicellular spheroids due to the possible cessation of transcellular delivery of nanoparticles in the apoptotic peripheral cells, caused by faster release of drugs from un-crosslinked micelles. Our results confirm the shape effect of nanoparticles on 2D models can vary from 3D models due to parameters such as spheroid penetration that can now play a pivotal role.