In vivo stability of protein coatings on poly lactic co glycolic nanoparticles

Submicron-sized poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) stabilised with bovine serum albumin (BSA) are dual radiolabelled using gamma emitters with different energy spectra incorporated into the core and coating. PLGA core is labelled by encapsulation of 111In-doped iron oxide NPs inside PLGA-NPs during NP preparation, while the BSA coating is labelled by electrophilic substitution using 125I. After intravenous administration into rats, energy-discriminant single-photon emission computerised tomography (SPECT) resolved each radioisotope independently. Imaging revealed different fates for the core and coating, with a fraction of the two radionuclides co-localising in the liver and lungs for long periods of time after administration, suggesting that NPs are stable in these organs. The general methodology reported here represents an excellent alternative for visualising the degradation process of multi-labelled NPs in vivo and can be extended to a wide range of engineered NPs.