Differences in Magnetic Particle Uptake by CNS Neuroglial Subclasses: Implications for Neural Tissue Engineering

Abstract

Materials and Methods: MP uptake and processing were studied in rat OPCs and oligodendrocytes, using fluorescence and transmission electron microscopy, and results collated with previous data from microglia and astrocytes.Results: Significant intercellular differences were observed between glial subtypes, with microglia demonstrating the most rapid/extensive particle uptake, followed by astrocytes, with OPCs and oligodendrocytes showing significantly lower uptake. Ultrastructural analyses suggest that MPs are extensively degraded in microglia but are relatively stable in other cells. Conclusions:Our findings have implications for use of the MP platform in a range of neural tissue engineering applications such as transfection, cell labeling and direct CNS biomolecule delivery.

‘Stealth’ nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics

“…For biological media, a 24 h time-point was included in the characterization as this was the total duration of cell exposure to particles, however endocytotic uptake of nanoparticles occurs much earlier, with particle internalization evident one-to-four hours post-particle addition, depending on cell type [22,46,47]. DLS measurements for CMX control and PEG nanoparticles within each cell-specific medium are shown in Table 1, and indicate colloidal stability within 24 h, consistent with previous findings addressing protein adsorption onto nanoparticles [48].…”

“…Of high relevance for clinical applications, PEG-coated nanoparticle accumulation is enhanced in pathological foci including gliosarcoma and Multiple Sclerosis models [17,18], possibly due to inflammation-induced BBB hyperpermeability -similar to enhanced nanoparticle permeability/retention (EPR effect) in brain tumors [19]. [20,21] exhibiting dramatically more rapid/extensive nanoparticle uptake than all other neural subtypes, in vitro [22] and in vivo [23]. This constitutes a significant 'extracellular barrier' to particle uptake by other neural cell types by 'out-competing' them [22].…”

“…[20,21] exhibiting dramatically more rapid/extensive nanoparticle uptake than all other neural subtypes, in vitro [22] and in vivo [23]. This constitutes a significant 'extracellular barrier' to particle uptake by other neural cell types by 'out-competing' them [22]. This differential uptake and competitive sequestration has profound implications for clinical nanoparticle therapies for neural applications.…”

Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy

“…We recently reported technically simple, rapid and safe magnetofection protocols for genetic modification of major neural transplant types including NSCs, with oscillating magnetic fields always outperforming static fields [21][22][23][24][25]. MNPs have emerged strongly as a class of advanced functional materials for neuro-regeneration, serving as 'multifunctional tools' for cell therapy given additional applications for non-invasive cell imaging and magnetic cell targeting, so it is clear that this non-viral gene transfer method offers significant benefits for clinical translation [26].…”

Part II: Functional delivery of a neurotherapeutic gene to neural stem cells using minicircle DNA and nanoparticles: Translational advantages for regenerative neurology

“…4 with oscillating magnetic fields can offer a safe solution for gene delivery in neural cells [15][16][17][18][19][20][21][22][23] but a major challenge encountered has been reduced transfection associated with increased size of therapeutic plasmids [23][24][25][26][27] (discussed in detail in Part I).…”