Radiolabeled Gold Nanoseeds Decorated with Substance P Peptides: Synthesis, Characterization and In Vitro Evaluation in Glioblastoma Cellular Models

Silva, Francisco; D’Onofrio, Alice; Mendes, Carolina; Pinto, Catarina; Marques, Ana; Campello, Maria Paula Cabral; Oliveira, Maria Cristina; Raposinho, Paula; Belchior, A.; Di Maria, Salvatore; Marques, Fernanda; Cruz, Carla; Carvalho, Josué; Paulo, António

Informações chave

Autores:

Silva, Francisco; D’Onofrio, Alice (Alice D' Onofrio); Mendes, Carolina; Pinto, Catarina; Marques, Ana; Campello, Maria Paula Cabral (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); Oliveira, Maria Cristina (Maria Cristina das Neves Oliveira); Raposinho, Paula (Paula Dolores Galhofas Raposinho); Belchior, A. (Ana Lúcia Vital Belchior); Di Maria, Salvatore (Salvatore di Maria); Marques, Fernanda (Fernanda Marujo Marques); Cruz, Carla; Carvalho, Josué; Paulo, António (António Manuel Rocha Paulo)

Publicado em

06/01/2022

Resumo

Despite some progress, the overall survival of patients with glioblastoma (GBM) remains extremely poor. In this context, there is a pressing need to develop innovative therapy strategies for GBM, namely those based on nanomedicine approaches. Towards this goal, we have focused on nanoparticles (AuNP-SP and AuNP-SPTyr8) with a small gold core (ca. 4 nm), carrying DOTA chelators and substance P (SP) peptides. These new SP-containing AuNPs were characterized by a variety of analytical techniques, including TEM and DLS measurements and UV-vis and CD spectroscopy, which proved their high in vitro stability and poor tendency to interact with plasma proteins. Their labeling with diagnostic and therapeutic radionuclides was efficiently performed by DOTA complexation with the trivalent radiometals 67Ga and 177Lu or by electrophilic radioiodination with 125I of the tyrosyl residue in AuNP-SPTyr8. Cellular studies of the resulting radiolabeled AuNPs in NKR1-positive GBM cells (U87, T98G and U373) have shown that the presence of the SP peptides has a crucial and positive impact on their internalization by the tumor cells. Consistently, 177Lu-AuNP-SPTyr8 showed more pronounced radiobiological effects in U373 cells when compared with the non-targeted congener 177Lu-AuNP-TDOTA, as assessed by cell viability and clonogenic assays and corroborated by Monte Carlo microdosimetry simulations.