Preparation, Characterization, Cytotoxicity and Biological Evaluation of ^99mTc-Doxorubicin-Epigallocatechingallate Functionalized Gold Nanoparticles as a New Generation of Theranostic Radiopharmaceutical

Abstract

Gold nanoparticles are currently used for the treatment of cancer through a myriad of modalities and delivery approaches. Conjugation of tumor imaging Single Photon Emitting Computed Tomographic (SPECT) radiopharmaceutical to gold nanoparticles will allow systemic targeting and imaging of cancer tissues simultaneously. In this study, gold nanoparticles (AuNPs) were prepared using Epigallocatechingallate (EGCG), loaded with doxorubicin (Dox), and characterized before and after doxorubicin conjugation. Cytotoxicity of EGCG-AuNPs and Dox-EGCG-AuNPs were evaluated against breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG-2) cell lines demonstrating high cytotoxic effects of Dox-EGCG-AuNPs against both cell lines. Doxorubicin was radiolabeled with 99mTc and our new approach has optimized various labeling conditions resulting in a radiochemical yield of 93.5 ± 2.04%. Biodistribution of 99mTc-Dox-EGCG-AuNPs was studied in normal and tumor bearing mice following I.V. and intratumoral injections at different time intervals. Results showed high uptake of the intravenously injected 99mTc-Dox-EGCG-AuNPs in tumor tissue (22.45 %ID/g at 2 h). In addition, localized intratumoral injection of 99mTc-Dox-EGCG-AuNPs showed extremely high levels of uptake in tumor (80.22 %ID/g at 15 min) with high retention for extended periods post injection. Our results present prospects for the utility of 99mTc-Dox-EGCG-AuNPs as a multiplexed theranostic agent through SPECT imaging of tumor tissue and therapy through photothermal destruction of cancer tissue through the application of exogenous laser lights as well as through tyrosine phosphatases inhibitor (through EGCG), and topoisomerase II inhibitor (through doxorubicin) effects.

Radiolabeled Gold Nanoparticles for Imaging and Therapy of Cancer

“…Biodistribution studies of the 99m Tc-labeled nanoparticles, performed in female albino Swiss mice having Ehrlich ascites carcinoma, showed a considerable tumour uptake of 22.45% ID/g after 2 h of intravenous injection. Furthermore, 99m Tc-gallic-AuNPs-DOX displayed a nearly 80% tumour retention upon intratumoural injection, at least for 2 h after administration [87][88][89].…”

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery

“…This radionuclide has been used extensively in nuclear medicine for the development of target-specific molecular imaging of alpha(v)beta(3) integrins, somatostatin receptors, gastrin releasing peptide receptors (GRPr), for sentinel node detection and a myriad of receptor positive tumors [ 15 , 16 , 17 , 18 , 19 , 20 ], as well as in imaging of cancers that overexpress Scavenger Receptor type B1 [ 21 ]. 99m Tc is also useful to follow the doxorubicin delivery from 99m Tc-DOX-loaded GA-Au NPs [ 22 ] and 99m Tc-Doxorubicin-Epigallocatechingallate functionalized gold nanoparticles [ 23 ]. In addition, 99m Tc can also be considered a theranostic radionuclide if its Auger electrons are emitted within the cell nucleus because, despite the low energy of its Auger electrons, they can be deposited in a very small area.…”