Quantitative to qualitative transition: comparison of in vitro and in vivo behavior and glioma-targeted delivery of PEGylated lipid-based nanoparticles

As a gold standard for lipid-based nanoparticles (LBNs), liposomes (Lips) have been clinically used for peripheral tumors but are not effective for tumors with intact barriers such as glioma. By increasing the proportion of polyethylene glycol (PEG) based on the formulation of Lips, a PEG-induced quantitative to qualitative transition from Lips to nanodiscs (NDs) and then to micelles (Mics) occurred. We found a contradiction that even though more Mics were taken up by cells than NDs and Lips, NDs showed the best barrier-crossing ability, with ligand modification causing further accumulation in the tumor site. In order to explain the phenomenon, we specifically established methods to investigate the in vitro and in vivo behavior, glioma targeting and the efficacy of different LBNs, demonstrating that NDs had advantages in multiple stages. Among different LBNs, NDs appeared promising for clinical translation with the formulation similar to Lips but superior in vivo performance. The methods we established might also be instructive for further understanding nanomedicines in the future.