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.

Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of alpha(v)beta(3) integrin, thereby inhibiting angiogenesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable multimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of 177Lu-AuNP-RGD in athymic mice bearing alpha(v)beta(3)-integrin-positive C6 gliomas and compare it with that of 177Lu-AuNP or 177Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-microPET/CT), histological characteristics and VEGF gene expression (by real-time polymerase chain reaction) in tumor tissues following treatment with 177Lu-AuNP-RGD, 177Lu-AuNP or 177Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, 1177Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 +/- 7.9 Gy). These results correlated with the observed therapeutic response, in which 177Lu-AuNP-RGD significantly (p < 0.05) induced less tumor progression, less tumor metabolic activity, fewer intratumoral vessels and less VEGF gene expression than the other radiopharmaceuticals, a consequence of high tumor retention and a combination of molecular targeting therapy (multimeric RGD system) and radiotherapy (177Lu). There was a low uptake in non-target organs and no induction of renal toxicity. 177Lu-labeled gold nanoparticles conjugated to cyclo-RGDfK(C) demonstrate properties suitable for use as an agent for molecular targeting radiotherapy.

The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target-specific molecular recognition. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been reported as high-affinity agents for the a(n)b(3) integrin. The aim of this research was to prepare a multimeric system of 177 Lu-labeled gold nanoparticles conjugated to c(RGDfK)C (cyclo(Arg-Gly-Asp-Phe-Lys)Cys) and to compare the radiation-absorbed dose with that of 177 Lu-labeled monomeric and dimeric RGD peptides to a(n)b(3) integrin-positive U87MG tumors in mice. DOTA-GGC (1,4,7,10-tetraazacyclododecane-N-N′,N 00 ,N 000 -tetraacetic acid-Gly-Gly-Cys) and c(RGDfK)C peptides were synthesized and conjugated to AuNPs by a spontaneous reaction of the thiol groups. Transmission electron microscopy, ultraviolet-visible, X-ray photoelectron spectroscopy, Raman and far-infrared spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. For the 177 Lu-AuNP-c(RGDfK)C to be obtained, the 177 Lu-DOTA-GGC radiopeptide was first prepared and added to a solution of AuNPs followed by c(RGDfK)C (25 ml, 5 mM) at 18 C for 15 min. 177 Lu-DOTA-GGC, 177 Lu-DOTA-cRGDfK and 177 Lu-DOTA-E-c(RGDfK) 2 were prepared by adding 177 LuCl 3 (370 MBq) to 5 ml (1 mg/ml) of the DOTA derivative diluted with 50 ml of 1 M acetate buffer pH 5. The mixture was incubated at 90 C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. Biokinetic studies were accomplished in athymic mice with U87MG-induced tumors. The radiochemical purity for all 177 Lu-RGD derivatives was 96 AE 2%. 177 Lu-absorbed doses per injected activity delivered to U87MG tumors were 0.357 AE 0.052 Gy/MBq (multimer), 0.252 AE 0.027 Gy/MBq (dimer) and 0.102 AE 0.018 Gy/MBq (monomer). 177 Lu-labeled dimeric and multimeric RGD peptides demonstrated properties suitable for targeted radionuclide therapy of tumors expressing a(n)b(3) integrins.

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The integration of fluorescence and plasmonic properties into one molecule is of importance in developing multifunctional imaging and therapy nanoprobes. The aim of this research was to evaluate the fluorescent properties and the plasmonic–photothermal, therapeutic, and radiotherapeutic potential of 177Lu–dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity (177Lu–DenAuNP–folate–bombesin) when it is internalized in T47D breast cancer cells. The intense near-Infrared (NIR) fluorescence emitted at 825 nm from the conjugate inside cells corroborated the usefulness of DenAuNP–folate–bombesin for optical imaging. After laser irradiation, the presence of the nanosystem in cells caused a significant increase in the temperature of the medium (46.8°C, compared to 39.1°C without DenAuNP–folate–bombesin, P < 0.05), resulting in a significant decrease in cell viability (down to 16.51% ± 1.52%) due to the 177Lu–DenAuNP–folate–bombesin plasmonic properties. After treatment with 177Lu–DenAuNP–folate–bombesin, the T47D cell viability decreased 90% because of the radiation-absorbed dose (63.16 ± 4.20 Gy) delivered inside the cells. The 177Lu–DenAuNP–folate–bombesin nanoprobe internalized in cancer cells exhibited properties suitable for optical imaging, plasmonic–photothermal therapy, and targeted radiotherapy.

The aim of this research was to evaluate the <em>in vitro</em> potential of ¹⁷⁷Lu-labeled gold nanoparticles conjugated to cyclo-[RGDfK(C)] peptides (¹⁷⁷Lu-AuNP-c[RGDfK(C)]) as a plasmonic photothermal therapy and targeted radiotherapy system in MCF7 breast cancer cells. Peptides were conjugated to AuNPs (20 nm) by spontaneous reaction with the thiol group of cysteine (C). After laser irradiation, the presence of c[RGDfK(C)]-AuNP in cells caused a significant increase in the temperature of the medium (50.5 °C, compared to 40.3 °C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with ¹⁷⁷-AuNP-c[RGDfK(C)], the MCF7 cell proliferation was significantly inhibited.

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The AuNP-octreotide system exhibited properties suitable for plasmonic photothermal therapy in the treatment of cervical cancer.