Dual T₁/T₂ Nanoscale Coordination Polymers as Novel Contrast Agents for MRI: A Preclinical Study for Brain Tumor

Abstract

In the last years, extensive attention has been paid on designing and developing functional imaging contrast agents for providing accurate non-invasive evaluation of pathology in vivo. However, the issue of false-positives or ambiguous imaging and the lack of a robust strategy for simultaneous dual-mode imaging remain to be fully addressed. One effective strategy for improving it is to rationally design magnetic resonance imaging (MRI) contrast agents (CAs) with intrinsic T 1 /T 2 dual-mode imaging features. In this work, the development and characterization of one-pot synthesized nanostructured coordination polymers (NCPs) which exhibit dual mode T 1 /T 2 MRI contrast behaviour is described. The resulting material comprises the combination of different paramagnetic ions (Fe 3+ , Gd 3+ , Mn 2+) with selected organic ligands able to induce the polymerization process and nanostructure stabilization. Among them, the Febased NCPs showed the best features in terms of colloidal stability, low toxicity, and dual T 1 /T 2 MRI contrast performance overcoming the main drawbacks of reported CAs. The dual-mode CA capability was evaluated by different means: in vitro phantoms, ex vivo and in vivo MRI, using a preclinical model of murine glioblastoma. Surprisingly, the in vivo MRI shows its T 1 and T 2 high contrast potential, allowing simultaneous recording of positive and negative contrast images in a very short period of time while being safer for the body. Moreover, the biodistribution assays reveals the persistence of the nanoparticles in the tumor and subsequent gradual clearance denoting their biodegradability. After a comparative study with commercial CAs, the results suggest these nanoplatforms as promising candidates for the development of dual-mode MRI CAs with clear advantages.

Silica Coated Iron/Iron Oxide Nanoparticles as a Nano-Platform for T2 Weighted Magnetic Resonance Imaging

“…Based on iron, these contrast agents, the ultimate fate of which is macrophage capture and subsequent metabolism into labile iron, are potentially less toxic than gadolinium based ones. Furthermore, as for many nanomaterials, their surface may be easily modified to offer longer circulating time, multimodality [6], modulable half-life or specificity [7,8], or to offer other functionalities such as drug delivery vehicles or magnetic and photonic ablation therapies [9][10][11], which is otherwise difficult to obtain with molecular contrast agents. However, large doses still need to be injected to afford a significant contrast, which raises toxicity concerns related to iron overload [2].…”

An Ultrahigh‐Field‐Tailored T1–T2 Dual‐Mode MRI Contrast Agent for High‐Performance Vascular Imaging

“…The r 2 / r 1 is calculated to be ≈5.50, indicating that P‐UDIOC can be used as an ideal T 1 – T 2 dual‐mode CA under UHF. [ 22,24 ] For comparison, we also investigated the imaging performances of a typical GBCA‐based T 1 CA, Gd‐DTPA, and a typical SPION‐based T 2 CA, MION with a hydrodynamic size of ≈20 nm (Figure S7, Supporting Information). The r 2 / r 1 values of Gd‐DTPA and MION are ≈1.29 and ≈29.56, respectively (Figure S8, Supporting Information), which are either too low or too high for T 1 – T 2 dual‐mode imaging.…”

“…The r 2 / r 1 values of Gd‐DTPA and MION are ≈1.29 and ≈29.56, respectively (Figure S8, Supporting Information), which are either too low or too high for T 1 – T 2 dual‐mode imaging. [ 22,24 ]…”

Coordination Polymers Integrating Metalloimmunology with Immune Modulation to Elicit Robust Cancer Chemoimmunotherapy

“…24,25 Previous studies have focused on the physicochemical property of metal unit in coordination polymers, such as magnetic properties for MRI imaging and Fenton activity for chemo-dynamic therapy. [26][27][28][29] However, metal ions detached from the intrinsically biodegradable coordination polymers would also take part in life processes, especially the immune system. [30][31][32] For instance, it has recently been reported that manganese ions and zinc ions could greatly enhance the Cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, and subsequently triggers multifaceted type I interferon-driven inflammatory responses to activate innate immune.…”