Neural stem cells (NSCs) present attractive natural drug
delivery
systems (DDSs). Their migratory potential enables crossing of the
blood–brain barrier and efficient and selective accumulation
near malignant cells. Here, we present the potential of NSCs as DDSs
for nucleoside analogue-conjugated nanogels (NGs). Two different approaches
were investigated: the intracellular loading and extracellular cell
surface decoration with NGs. For both designs, the tumor-specific
migratory potentials of NSCs remained unchanged; however, the intracellular
loading showed a shorter NG retention. The cell surface decoration
protocol yielded a high loading capacity of 100% after 1 h and a prolonged
drug retention. A redox-sensitive linker between NGs and the nucleoside
analogue 5-ethynyl-2′-deoxycytidine (EdC) allowed a tumor environment-specific
drug release and its efficient and preferential incorporation into
the DNA of the tumor cells. Interestingly, the tumor-trafficking potentials
of NSCs were significantly potentiated by irradiation of tumor cells.
In conclusion, this study indicates the potentials of cell surface-decorated
NSCs as DDSs for tumor-specific release, cellular uptake, and incorporation
of EdC into DNA.