Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors

Abstract

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non‐specificity, and low r1) that limit their applications. Herein, a wet‐chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES‐GON‐PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1‐weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM−1 s−1, and r2/r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2/r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES‐GON‐PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES‐GON‐PAA@RGD2) for T1‐weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αvβ3). The maximum signal enhancement (ΔSNR) for T1‐weighted MRI of tumors reaches up to 372 ± 56% at 2 h post‐injection of ES‐GON‐PAA@RGD2, which is much higher than commercial Gd‐chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES‐GON‐PAA@RGD2 with remarkable relaxivities is a promising and powerful T1‐weighted MRI contrast agent.

Iron Oxide Nanoparticles: An Alternative for Positive Contrast in Magnetic Resonance Imaging

“…Gadolinium oxide [4,5], gadolinium fluoride [6,7] and gadolinium phosphate [8] NPs have been synthesised and tried as T 1 contrast agents. Most recent examples are focused on targeted T 1 Gd 2 O 3 NPs [9], dual T 1 -T 2 MRI probes [10], hybrid MRI/fluorescent probes [11,12] and theranostic (theraphy + diagnostic) probes [13] for tumour imaging. A Gd 2 O 3 -NP hybrid CT/MRI probe functionalised with bisphosphonate was used by Mastrogiacomo et al to visualise calcium phosphate bone cement [14].…”

Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer

“…It could also be expected that the as-prepared NPs possess the potential to be applied as MRI imaging contrast agent due to the addition of Gd [32,33]. In vitro experiment demonstrated that T1 signal intensity was enhanced with the increasing concentration of HMON@ CuS/Gd solutions.…”

Recent advances in development of dendritic polymer‐based nanomedicines for cancer diagnosis

“…Dendritic polymers provide a great scaffold for holding paramagnetic ions (i.e., Gd 3+ , Mn 2+ ) (Connah & Angelovski, 2018), encapsulating magnetic oxides (i.e., Fe 3 O 4 , Gd 2 O 3 ) (Esmaeili et al, 2019) or accommodating other MRI probes (i.e., 19 F‐MRI nanoprobes, nitroxide radical units) (Celentano et al, 2020; Pinto et al, 2019). These systems not only significantly improve the blood circulation time and in vivo stability of contrast agents, but also increase their longitudinal relaxation efficacies and concentrations at local tumor sites, thereby enabling sensitive detection of early‐stage cancer and long‐term monitoring of cancer progression (Shen et al, 2019). Dendrimer‐based MR contrast agents for cancer diagnosis has been previously discussed in a few review papers (L. Ding, Lyu, et al, 2018; McMahon & Bulte, 2018).…”