Resumen:
The peptide-receptor radionuclide therapy (PRRT) is a successful approach for selectively
delivering radiation within tumor sites through specific recognition of radiolabeled peptides by
overexpressed receptors on cancer cell surfaces. The e cacy of PRRT could be improved by
using polymeric radio- and drug- therapy nanoparticles for a concomitant therapeutic e ect
on malignant cells. This research aimed to prepare and evaluate, a novel drug and radiation
delivery nanosystem based on the 177Lu-labeled polyamidoamine (PAMAM) dendrimer (DN)
loaded with paclitaxel (PTX) and functionalized on the surface with the Lys1Lys3(DOTA)-bombesin
(BN) peptide for specific targeting to gastrin-releasing peptide receptors (GRPr) overexpressed on
breast cancer cells. DN was first conjugated covalently to BN and DOTA (chemical moiety for
lutetium-177 complexing) and subsequently loaded with PTX. The characterization by microscopic
and spectroscopic techniques, in-vitro drug delivery tests as well as in in-vitro and in-vivo
cellular uptake of 177Lu-DOTA-DN(PTX)-BN by T47D breast cancer cells (GRPr-positive), indicated
the formation of an improved delivery nanosystem with target-specific recognition by GRPr.
Results of the 177Lu-DOTA-DN(PTX)-BN e ect on T47D cell viability (1.3%, compared with
10.9% of 177Lu-DOTA-DN-BN and 14.0% of DOTA-DN-(PTX)-BN) demonstrated the concomitant
radiotherapeutic and chemotherapeutic properties of the polymeric nanosystem as a potential agent
for the treatment of GRPr-positive tumors.