Protein release from PNIPAM-coated SPIONs. (a)
Schematic diagram
of protein entrapment and release by PNIPAM-coated SPIONs. (1) 1 μg
of protein was mixed with 1 mg of coated SPIONs above the LCST. Polymer
chains were collapsed around the nanoparticle core, and agitation
was used to avoid particle aggregation. (2) Upon cooling below the
LCST, the polymer shell expanded, and some protein molecules were
engulfed by the shell; we call this the entrapping state of the coated
SPION. (3) Following removal of excess protein by washes in the presence
of competing nonspecific proteins, entrapped proteins could be discharged
by polymer collapse above the LCST, (4) which permitted nonspecific
competitor proteins to replace the weakly bound cargo proteins, thereby
releasing them. (b) (Left) Western blot analysis of the apotransferrin
collected from the supernatant, following incubation of apotransferrin-loaded
PNIPAM-coated nanoparticles (1 mg) in the presence of 10 mg/mL RNase
B (the nonspecific competitor) at pH 7.5. SPIONs were briefly collected
on one side of the tube with a permanent magnet when the solution
was sampled at the indicated time points. (Right) Densitometry of
the apotransferrin immunoblot signal used to quantify the amount of
apotransferrin released. Error bars denote standard deviation, n = 3. 100% is the amount of protein used for entrapment,
given that the amount of protein detected in the washing steps prior
to release was negligible. (c) As in part b, but with or without application
of an alternating magnetic field (±MF as indicated) turned on
constantly for 10 min and then in pulses of 10 s on and 10 s off.
The bulk solution temperatures measured during magnetic heating using
an IR thermocouple probe are shown in parentheses above each time
point. The sample without magnetic heating was maintained at 21 °C.
Error bars denote standard deviation, n = 3. Input
lanes are from the same blot images but had to be moved because these
were not in lanes adjacent to the release samples. Therefore, a divider
line was introduced. Note that the double band of apotransferrin represents
differently glycosylated forms whose ratios are batch-dependent.