In this paper, we describe the synthesis of asymmetric functional POEGMA-b-P(ST-co-VBA) copolymers in methanol, yielding in onepot polymerization a range of nanoparticle morphologies, including spherical micelles, worm-like, rod-like micelles and vesicles. The presence of the aldehyde group was then exploited to form crosslinks or to conjugate chemotherapy compounds, such as doxorubicin, via pH-breakable bonds (Schiff base or imine) directly to the preformed nanoparticles. The influence of the nanoparticle morphologies on the MCF-7 breast cancer cell line uptake was investigated using flow cytometry and confocal microscopy. Finally, the IC 50 of DOX, following nanoparticle delivery, was studied showing significant influence of the nanoparticle carrier morphology on therapeutic efficacy for breast cancer.

Neurological disorders such as Alzheimer's disease, stroke, and brain cancers are difficult to treat with current drugs as their delivery efficacy to the brain is severely hampered by the presence of the blood-brain barrier (BBB). Drug delivery systems have been extensively explored in recent decades aiming to circumvent this barrier. In particular, polymeric nanoparticles have shown enormous potentials owing to their unique properties, such as high tunability, ease of synthesis, and control over drug release profile. However, careful analysis of their performance in effective drug transport across the BBB should be performed using clinically relevant testing models. In this review, polymeric nanoparticle systems for drug delivery to the central nervous system are discussed with an emphasis on the effects of particle size, shape, and surface modifications on BBB penetration. Moreover, the authors critically analyze the current in vitro and in vivo models used to evaluate BBB penetration efficacy, including the latest developments in the BBB-on-a-chip models. Finally, the challenges and future perspectives for the development of polymeric nanoparticles to combat neurological disorders are discussed.