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Multifunctional targeted therapy system based on 99m Tc/ 177 Lu‐labeled gold nanoparticles‐Tat(49–57)‐Lys 3 ‐bombesin internalized in nuclei of prostate cancer cells
Author(s) -
JiménezMancilla Nallely,
FerroFlores Guillermina,
SantosCuevas Clara,
OcampoGarcía Blanca,
LunaGutiérrez Myrna,
AzorínVega Erika,
IsaacOlivé Keila,
CamachoLópez Miguel,
TorresGarcía Eugenio
Publication year - 2013
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3087
Subject(s) - bombesin , chemistry , peptide , radionuclide therapy , prostate cancer , cancer cell , dota , photothermal therapy , receptor , chelation , cancer , biochemistry , nanotechnology , nuclear medicine , materials science , medicine , organic chemistry , neuropeptide
Radiolabeled gold nanoparticles may function simultaneously as radiotherapy and thermal ablation systems. The gastrin‐releasing peptide receptor (GRP‐r) is overexpressed in prostate cancer, and Lys 3 ‐bombesin is a peptide that binds with high affinity to the GRP‐r. HIV Tat(49–57) is a cell‐penetrating peptide that reaches the DNA. In cancer cells, 177 Lu shows efficient crossfire effect, whereas 99m Tc that is internalized in the cancer cell nuclei acts as an effective system of targeted radiotherapy because of the biological Auger effect. The aim of this research was to evaluate the in vitro potential of 99m Tc‐labeled and 177 Lu‐labeled gold nanoparticles conjugated to Tat(49–57)‐Lys 3 ‐bombesin peptides ( 99m Tc/ 177 Lu‐AuNP‐Tat‐BN) as a plasmonic photothermal therapy and targeted radiotherapy system in PC3 prostate cancer cells. Peptides were conjugated to AuNPs (5 nm) by spontaneous reaction with the thiol group of cysteine (Cys). The effect on PC3 cell viability after laser heating of the AuNP‐Tat‐BN incubated with the cancer cells was conducted using an Nd:YAG laser pulsed for 5 ns at 532 nm (0.65 W/cm 2 ). For the 99m Tc/ 177 Lu‐AuNP‐Tat‐BN to be obtained, the 177 Lu‐DOTA‐Gly‐Gly‐Cys and 99m Tc‐HYNIC‐octreotide radiopeptides were first prepared and added simultaneously to a solution of AuNP‐Tat‐BN. 99m Tc/ 177 Lu‐AuNP‐Tat‐BN (20 Bq/cell) was incubated with PC3 cells, and the effect on the cell proliferation was evaluated after 3 days. Fluorescence images of 99m Tc/ 177 Lu‐AuNP‐Tat‐BN internalized in nuclei of PC3 were also obtained. After laser irradiation, the presence of AuNP‐Tat‐BN caused a significant increase in the temperature of the medium (46.4 vs 39.5 °C of that without AuNP) resulting in a significant decrease in PC3 cell viability down to 1.3%. After treatment with 99m Tc/ 177 Lu‐AuNP‐Tat‐BN, the PC3 cell proliferation was inhibited. The nanosystem exhibited properties suitable for plasmonic photothermal therapy and targeted radiotherapy in the treatment of prostate cancer.