Tumor Targeting Effect of Triphenylphosphonium Cations and Folic Acid Coated with Zr-89-Labeled Silica Nanoparticles

Abstract

In this study, we investigated the tumor targeting effect in cancer cells using triphenylphosphonium (TPP) cations, which are accumulated by differences in membrane potential, and folic acid (FA), which is selectively bound to overexpressed receptors on various cancer cells. We used Food and Drug Administration (FDA)-approved silica nanoparticles (SNPs) as drug carriers, and SNPs conjugated with TPP and FA (STFs) samples were prepared by introducing different amounts of TPP and FA onto the nanoparticle surfaces. STF-1, 2, 3, 4 and 5 are named according to the combination ratio of TPP and FA on the particle surface. To confirm the tumor targeting effect, 89Zr (t1/2 = 3.3 days) was coordinated directly to the silanol group of SNP surfaces without chelators. It was shown that the radiochemical yield was 69% and radiochemical purity was >99%. In the cellular uptake evaluation, SNPs with the most TPP (SFT-5) and FA (SFT-1) attached indicated similar uptake tendencies for mouse colon cancer cells (CT-26). However, the results of the cell internalization assay and measurement of positron emission tomography (PET) images showed that SFT-5 had more affinity for the CT-26 tumor than other samples the TPP ratio of which was lower. Consequently, we confirmed that TPP ligands affect target cancer cells more than FA, which means that cell membrane potential is significantly effective for tumor targeting.

Synthesis of Hyaluronic Acid-Conjugated Fe3O4@CeO2 Composite Nanoparticles for a Target-Oriented Multifunctional Drug Delivery System

“…89 Zr has a relatively low positron energy of 395.5 keV and a half-life of 78.4 h, which makes it safer to manage and dispose of in clinics, easier to produce and more stable in vivo. As such, using it for high-resolution, quantitative imaging through PET is much more effective than using 124 I to treat tumors [ 24 , 25 , 26 ]. When radionuclides are released, 89 Zr can accumulate in bones or bind to plasma proteins, so the release of 89 Zr must be prevented.…”

Long-Term Tumor-Targeting Effect of E. coli as a Drug Delivery System

“…In the case of tumors, 89 Zr-labeled E. coli accumulation was observed to increase, and the tumor/liver ratio was also confirmed to continuously increase for 6 days. Dissociated 89 Zr has been reported to accumulate in bones in the body [ 31 , 32 , 33 ]. Nevertheless, bone accumulation by 89 Zr was not observed, as seen in Figure 7 , so it is not dissociated from E. coli after intravenous injection in the body, and this result is associated with high in vitro labeling stability ( Figure 4 b).…”

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

“…Folate receptor, a glycosyl-phosphatidyl-inositol anchored on the cell surface, is overexpressed in most cancers, enabling their targeting by functionalization of the nanocarrier with folic acid (FA) [ 240 , 241 , 242 , 243 , 244 , 245 ]. Functionalization with FA improved the specific delivery to cancer cells and also had a combined chemo/magnetothermal therapeutic effect [ 90 , 202 , 246 , 247 , 248 , 249 , 250 , 251 ]. FA was employed as the main targeting ligand in the development of a drug delivery system for colchicine, which is highly cytotoxic.…”