Publication Details (including relevant citation information):
J. Mater. Chem., 2012,22, 20423-20433
Stabilization of proteins against thermal deactivation is a major challenge, and a simple, facile, novel chemical approach is described here to overcome this hurdle. We report here, for the first time, the successful synthesis of ultrastable protein nanoparticles consisting of met-hemoglobin (Hb) conjugated with low molecular weight polyacrylic acid (PAA, Mw 8000) to form discrete nanoparticles. Hb–PAA nanoparticles were not deactivated when subjected to prolonged thermal treatment such as steam sterilization conditions (122 °C, 40 minutes, 17–20 psi), while the unprotected Hb lost most of its activity when subjected to the same heating conditions. Several Hb–PAA derivatives which resist thermal inactivation, in a similar manner, are produced and characterized. Interestingly, the highest activity retention, after the above thermal treatment, was 100% for the untreated samples. This resistance to heat is attributed to the enhanced thermodynamic stability of the Hb–PAA conjugate and improved re-folding of the denatured state to the native form, facilitated by PAA conjugation to Hb. This is a unique approach to stabilize Hb against thermal inactivation, and it is a major breakthrough in the production of stable Hb-based nanomaterials that can be safely sterilized in an autoclave for biomedical/in vivo applications.