title: Interrogating the Role of Receptor-Mediated Mechanisms: Biological Fate of Peptide-Functionalized Radiolabeled Gold Nanoparticles in Tumor Mice.
abstract: To get a better insight on the transport mechanism of peptide-conjugated nanoparticles to tumors, we performed in vivo biological studies of bombesin (BBN) peptide functionalized gold nanoparticles (AuNPs) in human prostate tumor bearing mice. Initially, we sought to compare AuNPs with thiol derivatives of acyclic and macrocyclic chelators of DTPA and DOTA types. The DTPA derivatives were unable to provide a stable coordination of (67)Ga, and therefore, the functionalization with the BBN analogues was pursued for the DOTA-containing AuNPs. The DOTA-coated AuNPs were functionalized with BBN[7-14] using a unidentate cysteine group or a bidentate thioctic group to attach the peptide. AuNPs functionalized with thioctic-BBN displayed the highest in vitro cellular internalization (≈ 25%, 15 min) in gastrin releasing peptide (GRP) receptor expressing cancer cells. However, these results fail to translate to in vivo tumor uptake. Biodistribution studies following intravenous (IV) and intraperitoneal (IP) administration of nanoconjugates in tumor bearing mice indicated that the presence of BBN influences to some degree the biological profile of the nanoconstructs. For IV administration, the receptor-mediated pathway appears to be outweighed by the EPR effect. By contrast, in IP administration, it is reasoned that the GRPr-mediated mechanism plays a role in pancreas uptake.
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa , Lisbon, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Silva
authors.forename: Ajit
authors.initials: A
authors.lastname: Zambre
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa , Lisbon, Portugal.
authors.forename: Maria Paula Cabral
authors.initials: MP
authors.lastname: Campello
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa , Lisbon, Portugal.
authors.forename: Lurdes
authors.initials: L
authors.lastname: Gano
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa , Lisbon, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Santos
authors.affiliation: Centro de Química-Física Molecular, Instituto Superior Técnico, Universidade de Lisboa , Lisbon, Portugal.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Ferraria
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa , Lisbon, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Ferreira
authors.forename: Amolak
authors.initials: A
authors.lastname: Singh
authors.forename: Anandhi
authors.initials: A
authors.lastname: Upendran
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa , Lisbon, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Paulo
authors.forename: Raghuraman
authors.initials: R
authors.lastname: Kannan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism*
chemical_list: D006046:Gold