Changing Surface Polyethylene Glycol Architecture Affects Elongated Nanoparticle Penetration into Multicellular Tumor Spheroids

Nanoparticles (NPs) designed for biomedical applications are coated with protein-repellent polymers. Here, we examine the penetration of rodlike NPs with narrow size distributions (L-n = 170 nm, w(n) = 12 nm) into multicellular tumor spheroids prepared from two human cancer cell lines. Two types of NPs with different core materials [polyferrocenylsilane and cellulose nanocrystals (CNC)] were coated with a dense brush of poly(oligoethyleneglycol methacrylate) (POEGMA), while a second CNC NP sample was coated with a linear polyethylene glycol (PEG) brush. While the core material had little influence, the coating material was strikingly important, with POEGMA-coated NPs penetrating much more deeply into the tumor spheroids than the NPs coated with linear PEG. Localization experiments using 111In-labeled POEGMA-coated CNC NPs showed that most of the radioactivity remained in the interstitial space (ca. 78%) with little cell uptake (ca. 6%). Hence, the deep penetration of these nanorods into tumor spheroids is associated with an interstitial diffusion pathway through the extracellular matrix and not cellular transcytosis.

Automated summary

The study shows that nanoparticles coated with poly(oligoethyleneglycol methacrylate) (POEGMA) can penetrate deeper into tumor spheroids compared to nanoparticles coated with linear polyethylene glycol (PEG). The penetration is associated with interstitial diffusion through the extracellular matrix.