Synthesis, Characterization, and Enhanced Cancer‐Imaging Application of Trans‐activator of Transcription Peptide‐conjugated Ultrasmall Gadolinium Oxide Nanoparticles

Abstract

We prepared gadolinium oxide (Gd2O3) nanoparticles (GNPs) coated with a trans‐activator of transcription (TAT) peptide with cell‐penetrating ability (i.e., TAT‐GNPs) through one‐pot process. We characterized the particle diameter, surface‐coating structure, water proton relaxivities, and in vitro cellular toxicities of the TAT‐GNPs. We measured in vivo T1 magnetic resonance images (MRI) in a model nude mouse with liver cancer prior and posterior to intravenous administration. The average particle diameter of the GNPs was 1.5 nm. The sample solution exhibited a longitudinal water proton relaxivity (r1) of 18.2/s/mM (r2/r1 = 1.6, r2 = transverse water proton relaxivity), which is four to five times higher than those of commercial Gd‐chelates. The in vivo T1 MRI exhibited positively (or T1) enhanced contrasts in the mouse liver cancer after intravenous administration, demonstrating that the TAT‐GNPs acted as an enhanced cancer‐imaging agent similar to the cancer‐targeting agent in T1 MRI.

Recent Advances in Gadolinium Based Contrast Agents for Bioimaging Applications

“…Gd-NPs coated with trans-activator of transcription (TAT) peptide with the cell-penetrating ability (i.e., TAT-Gd-NPs) were synthesized through a one-pot process exhibiting r 1 value greater than those of commercial Gd-chelates. Synthesized TAT-Gd-NPs possessed the d avg of 1.5 nm with a r 1 of 18.2 s −1 ·mM −1 and r 2 /r 1 = 1.6 [ 112 ]. There are several cancer-related proteins that are abundantly present in the tumor extracellular matrix.…”

Functionalized Lanthanide Oxide Nanoparticles for Tumor Targeting, Medical Imaging, and Therapy

“…Ln 2 O 3 nanoparticles synthesized via the polyol method generally have ultrasmall diameters (average particle diameter = 2.0 nm) [39][40][41][42][43][44]. Figure 4a-c shows various HRTEM images of Gd 2 O 3 nanoparticles [44,47,48]. Both particle and hydrodynamic diameters follow a log-normal function distribution; therefore, average particle and hydrodynamic diameters can be obtained by fitting the log-normal distribution function to the observed particle and hydrodynamic diameter distributions, respectively.…”

“…This experiment shows the good colloidal dispersion of the nanoparticles in aqueous media. Reproduced from [44,47,48]. Copyright 2020 The Royal Society of Chemistry [44]; Copyrights 2018 Wiley [47,48].…”

“…Reproduced from [44,47,48]. Copyright 2020 The Royal Society of Chemistry [44]; Copyrights 2018 Wiley [47,48].…”

“…The spectrum of the PAA-coated Gd2O3 nanoparticles exhibited a series of bands stemming from PAA, such as C−H stretching (2930 cm −1 ), COO − antisymmetric stretching (1550 cm −1 ), and COO − symmetric stretching vibrations (1400 cm −1 ). The PAA and the [44,47,48]. Arrows and circles indicate nanoparticles.…”