Fluorescent, Plasmonic, and Radiotherapeutic Properties of the 177Lu-Dendrimer-AuNP-Folate-Bombesin Nanoprobe Located Inside Cancer Cells.

Héctor Mendoza-Nava,Clara Santos-Cuevas,Blanca Ocampo-García,Myrna Luna-Gutiérrez,Guillermina Ferro-Flores,Nallely Jiménez-Mancilla,Keila Isaac-Olivé,Flor De María Ramírez,Erika Azorín-Vega

doi:10.1177/1536012117704768

Abstract

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.

Highlights

Different-sized gold nanoparticles (AuNPs) can be classified into molecular luminescent AuNPs and conventional plasmonic AuNPs.[1]
The cells were routinely cultured at 37C with 5% CO2 and 85% humidity in Roswell Park Memorial Institute medium (SigmaAldrich Co) supplemented with 10% fetal bovine serum and antibiotics (100 U/mL penicillin and 100 mg/mL streptomycin). These cells were selected since previously we have demonstrated an important uptake of 177Lu–DenAuNP–folate–bombesin in T47D, which was significantly inhibited by preincubation with cold Lys3-bombesin peptide or folic acid alone, indicating that the multifunctional system has specific recognition for GRP receptors (GRPR) and folate receptor (FR).[20]
This specific recognition and internalization into the cell cytoplasm is attributed to the biological behavior conferred by bombesin and folate on the dendrimer surface which binds to GRPR and FR on the cell membrane.[20,23]

Summary

Introduction

Different-sized gold nanoparticles (AuNPs) can be classified into molecular luminescent AuNPs (from 0.3 to 2 nm) and conventional plasmonic AuNPs (from 2 to 100 nm).[1] Luminescent AuNPs lack the characteristic surface plasmon resonance (SPR) due to the limited number of free electrons but can give a broad range of emissions from visible to near-Infrared (NIR) regions.[1] Due to their SPR, AuNPs can be used as localized heat sources for cancer treatment.[2,3] The photothermal conversion effect in AuNPs is based on the collective oscillations of the electrons under optical excitation, which provide strong localized heating when they are irradiated with a laser or exposed to a certain radiofrequency field.[3,4,5] The localized heating, reaching temperatures about of 700C around AuNPs, causes irreversible thermal destruction of cancer tissues.[6,7,8].

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