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

Autor: Sang Wook Kim, Jeong Hoon Park, Jun Young Lee, Pyeong Seok Choi, Gun Gyun Kim
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Cell
PET imaging
Pharmaceutical Science
Nanoparticle
02 engineering and technology
silica nanoparticles
Analytical Chemistry
Mice
Drug Discovery
Receptor
Internalization
media_common
Membrane potential
Mice
Inbred BALB C

0303 health sciences
Chemistry
Silicon Dioxide
021001 nanoscience & nanotechnology
medicine.anatomical_structure
Chemistry (miscellaneous)
Colonic Neoplasms
Molecular Medicine
Female
Zr-89
0210 nano-technology
Drug carrier
media_common.quotation_subject
Conjugated system
Article
lcsh:QD241-441
03 medical and health sciences
folic acid
Organophosphorus Compounds
lcsh:Organic chemistry
Cations
medicine
Animals
Humans
Physical and Theoretical Chemistry
030304 developmental biology
Radioisotopes
Organic Chemistry
Positron-Emission Tomography
Cancer cell
Nanoparticles
Zirconium
Radiopharmaceuticals
triphenylphosphonium cation
surface modification
Nuclear chemistry
Zdroj: Molecules, Vol 25, Iss 2922, p 2922 (2020)
Molecules
Volume 25
Issue 12
ISSN: 1420-3049
Popis: 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.
Databáze: OpenAIRE