Visualisation of dual radiolabelled poly(lactide-co-glycolide) nanoparticle degradation in vivo using energy-discriminant SPECT

Autor: Carlos Pérez-Campaña, Marco Marradi, Pengfei Jiang, Shan Yu, Jordi Llop, Congjie Gao, Zuriñe Baz, Boguslaw Szczupak, Maria Puigivila, Sergio Moya, María Echeverría, Vanessa Gómez-Vallejo, Zhengwei Mao
Rok vydání: 2015
Předmět:
Popis: The determination of nanoparticle (NP) stability and degradation in vivo is essential for the accurate evaluation of NP biodistribution in medical applications and for understanding their toxicological effects. Such determination is particularly challenging because NPs are extremely difficult to detect and quantify once distributed in a biological system. Radiolabelling with positron or gamma emitters and subsequent imaging studies using positron emission tomography (PET) or single-photon emission computerised tomography (SPECT) are some of the few valid alternatives. However, NPs that degrade or radionuclides that detach or are released from the NPs can cause artefact. Here, submicron-sized poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) stabilised with bovine serum albumin (BSA) were dual radiolabelled using gamma emitters with different energy spectra incorporated into the core and coating. To label the core, 111In-doped iron oxide NPs were encapsulated inside PLGA-NPs during NP preparation, and the BSA coating was labelled by electrophilic substitution using 125I. After intravenous administration into rats, energy-discriminant 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. Organ harvesting followed by gamma counting corroborated the SPECT results. 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.
Databáze: OpenAIRE