Functional Magnetic Nanoparticles for Protein Delivery Applications

Iron oxide nanoparticles (IONPs) surface functionalised with thermo-responsive polymers present a potential strategy for biomolecule delivery and release. Here, the synthesis of thermo-responsive poly-N-isopropylmethacrylamide (PNIPMAM) coated IONPs is reported. The lower critical solution temperature (LCST) of the polymer-shell NP was tuned by using different chain length PNIPMAM shell (7.5 – 89 kDa) on the NP core (15.4 ± 2.1 nm IONPs). The LCST of all the core-shell nanostructures was above 37 °C, where the LCST of 40 kDa PNIPMAM @ 15.4 ± 2.1 nm IONPs was ~ 45 °C. These core-shell NPs were then screened for their magnetic heating behaviour where 40 kDa PNIPMAM @ 15.4 ± 2.1 nm IONPs showed maximum heating with a specific absorption rate (SAR) value of ~ 7.5 W/g (magnetic field strength = 28.7 mT, and frequency = 102.4 kHz). After LCST and magnetic heating characterization, these core-shell NPs were screened for the encapsulation/triggered release of a model protein apotransferrin (TRF). The protein release was observed in the presence of a competitor protein (RNaseB) where, 40 kDa PNIPMAM @ 15.4 ± 2.1 nm IONPs displayed a good TRF release profile (45 °C) with minimum protein leak at 37 °C. After the optimization of
the core-shell nanostructure for TRF encapsulation/triggered release, effect of competitor protein properties (size and glycosylation) was studied on the triggered TRF release. Glycosylated protein competitor (RNaseB) released ~ 20 ng of the encapsulated TRF (~ 400 ng) compared with the similar size (~ 14 KDa) non-glycosylated RNaseA (~ 2 ng). Additionally, bigger glycosylated proteins than RNaseB were better competitors for the triggered TRF release (~ 170 ng, ovalbumin ~ 45 KDa). Serum was also tested as a source of competitor proteins for the magneto-thermal protein release. Magnetic heating, through a pulsed
application resulted in a faster protein release as compared to the conventional heating of the protein loaded PNIPMAM @ IONPs. Hence the developed thermo-responsive core-shell NP could be a potential tool for the in vivo biomolecule delivery/temperature-sensitive release.