Following extensive research in the field of bionano-interfaces, it is now well understood that the primary interaction of biological species – such as cells – with nanoparticles is strongly dependent to the long-lived protein corona, i.e. a strongly adsorbed protein layer at the surface of nanoparticles. The amount, composition, and exposure site of the associated proteins in the long-lived protein corona can define the biological response to the nanoparticles and hence reveal their biological fate.
Scientists have now shown that laser plasmonic heat induction leads to significant changes in the protein corona composition at the surface of gold nanorods. These results are important for in vivo applications of plasmonic and magnetic nanoparticles.
“More specifically, we identified several proteins in the corona whose concentrations varied most substantially due to the photo-induced (plasmonic) heating vs. simple thermal heating,” Morteza Mahmoudi, a professor at Tehran University of Medical Sciences, who heads the Laboratory of Nano-Bio Interactions, explains to Nanowerk. “Our results may define new in vivo applications for nanoparticles with hyperthermia capability and better define the likely interactions of cells with nanoparticles after photo-induced plasmonic heating.”
The researchers, which besides Mahmoudi’s team included Professor Kenneth Suslick’s group at the University of Illinois at Urbana-Champaign, reported their findings in the December 12, 2013 online edition of Nano Letters (“Variation of Protein Corona Composition of Gold Nanoparticles Following Plasmonic Heating”).
One of the key conclusions from this work is that potential changes in the protein corona, following hyperthermia/photo-induced treatment, may influence the final biological fate of plasmonic and magnetic nanoparticles in clinical applications and also help elucidate safety considerations for hyperthermia applications.
UV-vis absorption spectra and transmission electron micrographs of gold nanorods (AuNR)-protein complexes before and after laser irradiation or thermal treatment at 45 °C for 55 min. (A) UV-vis spectra for AuNRs after 10% fetal bovine serum (FBS) exposure, followed by hyperthermia treatment. (B) UV-vis spectra for AuNRs after 100% FBS exposure, followed by hyperthermia treatment. (C,D) TEM images of cetyltrimethylammonium bromide (CTAB)-AuNRs. (E) TEM image of a protein-AuNR complex (10% FBS). (F) TEM image of protein-AuNR complex (100% FBS). (Reprinted with permission from American Chemical Society)
In a previous Nanowerk Spotlight (“Biological responses to nanoparticles are temperature-dependant”) we reported on Mahmoudi’s work that showed that changes in the incubation temperature of proteins and nanoparticles can cause significant effects in protein corona formation and composition.
“The variation of incubating temperature leads to various biological responses – e.g. cell uptake – to the corona coated nanoparticles incubated at different temperatures,” says Mahmoudi. “Contrary to this conventional thermal heating of nanoparticles-protein complexes, in our new report, we proved that plasmonic heating induces a substantial temperature gradient that starts at the surface of gold nanorods and decays with distance.”
He notes that, although the solution temperature is uniform over the course of either thermal or photo-induced heating experiments, one could expect the heating process is different in the two situations, mainly due to the fact that heating during plasmonic activation begins on the surface of a nanoparticle (heating from the inside out, where the local temperature at the surface of the laser-activated nanoparticles can be substantially higher than the temperature of the remainder of the solution), while conventional thermal heating occurs from the outside in.
Besides the fascinating physical phenomena – i.e. the oscillating electric fields by light leading to the heat induction – at the surface of plasmonic nanoparticles, these particles, such as gold and silver, have numerous applications in medical sciences such as chemical and biological sensing/imaging, photothermal cancer therapy, and photothermal drug release.
In addition to plasmonic nanoparticles, magnetic nanoparticles (e.g. superparamagnetic iron oxide nanoparticles) have extensive hyperthermia applications, which are now in preclinical stage. Mahmoudi points out that the results of their work can lead to a deep understanding on how the variation of the protein corona on the surface of these plasmonic and magnetic nanoparticles, following heat induction, is crucial to either increasing their therapeutically yield or predicting their biological fate/toxicity.
“As the in vivo capture of nanoparticles from biological fluids/species – such as blood plasma – is not performed yet, future work could be focused on exploring protein corona in vivo,” Mahmoudi describes the team’s next steps. “In addition, there are very few techniques for real-time in situ analysis of protein-nanoparticle complexes, therefore, one can look forward to see the emergence of new instruments for such real-time in situ analysis of the protein corona.”