Amphiphilic cyclodextrin-based nanocarriers for magnetic delivery of a morphogen in microfluidic environments

Abstract

Reliable methodologies for spatio-temporal controlled delivery of morphogens are of key importance in organoid research, regenerative medicine and developmental biology. To develop such a methodology, we constructed a magnetic nanocarrier composed of a supramolecular nanoassembly of amphiphilic cyclodextrin (SC6OH) entangling superparamagnetic iron oxide nanoparticles (SPIONs) within the surface. Upon encapsulation of a defined amount of retinoic acid (RA), the nanocarriers are remotely guided through microfluidic channels to a cell culture compartment by a specifically designed magnetic device based on electro-mechanically actuated permanent magnets. We demonstrate the efficiency of this innovative technology for the delivery of morphogens by applying it to induce the differentiation of human neuroblastoma SH-SY5Y cells into neurons. The magnetically controlled RA delivery resulted in the successful induction of neuronal differentiation with precise spatial and temporal control while minimizing reliance on complex microfluidic setups. Thus, the integration of magnetic actuation with supramolecular nanocarriers promotes new efficient routes and scalable protocols that go beyond state-of-the-art research in various bio-medical applications.