Long-term magnetothermal neurostimulation in vivo
To evaluate the potential of long-term and repeated
neuromodulation using FVIOs, fear behavior testing in mice was conducted
over 60 days. As shown in Fig. 7a, the FVIOs retained the ability to
magnetothermally elicit freezing behaviors in mice on the
60th day. However, no significant changes in
percentage of freezing time were observed among the SPIO (0.8
μg)-treated mice, which may be due to SPIO biodegradation in the CeA. To
confirm this, 7-Tesla magnetic resonance imaging (MRI) was employed to
evaluate the changes in the concentrations of the magnetic nanoheaters
in the CeA regions on the 1st, 30th, and 60th days using ultrashort echo
time (UTE) pulse sequences. Linear correlations of the transverse
relaxation rates (1/T2 values) of the FVIOs and SPIOs
were first obtained (Figure S11, Supporting Information). Figure 7b
presents MR images of mouse brains with which the concentrations of
FVIOs and SPIOs that remained in the CeA regions could be determined
(marked with yellow arrows) on the 1st,
30th, and 60th days. The relative
signal intensity of the FVIOs measured in the CeA remained stable for 60
days (Figure 7c), suggesting that the amount of FVIOs remained unchanged
at the injection site. However, the SPIO signal in the CeA notably
decreased on the 60th day, indicating their
disappearance. The disappearance of the SPIOs is mainly ascribed to
their smaller size in comparison with the FVIOs, which makes their
biodegradation and diffusion easier. In contrast, the FVIOs
were highly stable under physiological conditions, giving them great
potential for long-term and repeated neural stimulation and
therapy[55].