Remote-controlled, bio-compatible, multifunctional nanoreservoirs: A potential nanoplatform for regulating axon extension and facilitating imaging in growing neurons
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Traumatic injury to the central nervous system (CNS) is a significant health problem and, currently, there is no effective treatment, partly because of the complexity of the CNS. Biocompatible nanovectors that can be remotely actuated hold promise for delivering treatments targeted to specific neurons for enhancing neurite growth and synaptogenesis after injury. Furthermore, assessing the efficacy of treatments could be enhanced by biocompatible nanovectors designed for imaging in vivo. To address this need, we constructed and tested the biocompatibility of two nanoparticle systems. The first was designed to deliver axon growth-promoting drugs to specific neurons and was based on ferromagnetic and superparamagnetic iron oxide nanoparticles in a thermo-activated polyethylene glycol (PEG) network. These particles were synthesized by encapsulating iron oxide nanoparticles in PEG analogue biopolymers using free radical polymerization. The resulting nanospheres were 300 ± 50 nm in diameter and displayed a broader range for volumetric transition when placed in oscillating magnetic fields compared to previously constructed drug delivery systems. Particles imbibed with vitamin B12 released this substance in a controlled way when magnetically actuated. When tested in PC12 cells, the constructed nanoparticles had minimal toxicity with iron concentrations up to 3.4 mM when measured using a live/dead assay. Cells exposed to ferromagnetic particles displayed morphology and neurite outgrowth similar to untreated cells. The second nanoparticle system was synthesized by encasing cadmium telluride (CdTe) semiconductor quantum dots (QDs) in a thermo-sensitive poly (N-isopropylacrylamide) (PNIPAM) network. Similar to the magnetically-responsive system, these nanospheres also acted as a reservoir for drug molecules. When heated above the lower critical solution temperature (LCST, ∼33°C), the QD-containing nanospheres shrank. In PC12 cells, these PNIPAM nanospheres (up to 500 μg/ml PNIPAM) did not increase toxicity or decrease neurite outgrowth compared to untreated cells. In addition, QD-based nanospheres with carboxylic rich CdTe surfaces localized to the cell nucleus. Thus, the two nanoscale systems constructed and tested here represent potential drug-delivery/imaging systems with improved biocompatibility; cell targeting and drug release profiles compared to previously reported systems, suggesting increased therapeutic potential for treating CNS lesions.