PhD in Engineering of Multi-Targeting Nanoparticles for Enhanced Brain Cell Delivery and Uptake

This PhD project at the University of Manchester, in partnership with the University of Helsinki, focuses on the development of biomimetic hybrid nanoparticles to address major challenges in brain drug delivery. The research aims to engineer nanoparticles by combining cell membrane fragments with functionalized lipids, creating customizable surface ligands that enhance targeting of brain cells, facilitate transport across the blood–brain barrier (BBB), and ensure efficient cytoplasmic release of therapeutic molecules, including nucleic acids. The project addresses the limitations of current nanoparticles, which often interact non-specifically with healthy tissues, fail to cross the BBB, and become trapped in endosomes, thus limiting their effectiveness in treating central nervous system (CNS) diseases such as Alzheimer’s and glioblastoma. The main objectives are to develop and characterize hybrid nanoparticles with tunable ligand profiles, investigate their cellular uptake and intracellular trafficking, assess endosomal escape and cytoplasmic delivery, and evaluate BBB transport using advanced in vitro multicellular models. The methodology integrates nanoparticle design, cell biology, and bioengineering. The candidate will fabricate and characterize nanoparticles using techniques such as dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM), and study their biological behavior through confocal microscopy, flow cytometry, and live-cell imaging. Advanced in vitro fluidic BBB models will be used to analyze nanoparticle transcytosis and delivery efficiency. The project is jointly supervised by Dr Christos Tapeinos and Dr Ayse Latif at the University of Manchester, and Associate Professor Shiqi Wang at the University of Helsinki. The student will spend 12 months in Helsinki for advanced training in cellular uptake and cytoplasmic delivery studies, with the remainder of the time in Manchester focusing on nanoparticle development and BBB modeling. The research is supported by the EPSRC HALO National Hub for Advanced Long-acting Therapeutics and grants from the Research Council of Finland and the ERC Starting Grant. Full funding is provided for tuition and a stipend at the UKRI rate for four years, but candidates must cover relocation and visa costs. Applicants should have a strong academic background in relevant fields and a motivation for interdisciplinary research. The application process requires contacting both main supervisors before applying, and submitting all required documents via the online portal.