Magnetic Resonance Diagnosis of Early Triple-Negative Breast Cancer Based on the Ionic Covalent Organic Framework with High Relaxivity and Long Retention Time

Abstract

Patients with triple-negative breast cancer (TNBC) have dismal prognoses due to the lack of therapeutic targets and susceptibility to lymph node (LN) metastasis. Therefore, it is essential to develop more effective approaches to identify early TNBC tissues and LNs. In this work, a magnetic resonance imaging (MRI) contrast agent (Mn-iCOF) was constructed based on the Mn­(II)-chelated ionic covalent organic framework (iCOF). Because of the porous structure and hydrophilicity, the Mn-iCOF has a high longitudinal relaxivity (r 1) of 8.02 mM–1 s–1 at 3.0 T. For the tumor-bearing mice, a lower dose (0.02 mmol [Mn]/kg) of Mn-iCOF demonstrated a higher signal-to-noise ratio (SNR) value (1.8) and longer retention time (2 h) compared to a 10-fold dose of commercial Gd-DOTA (0.2 mmol [Gd]/kg). Moreover, the Mn-iCOF can provide continuous and significant MR contrast for the popliteal LNs within 24 h, allowing for accurate evaluation and dissection of LNs. These excellent MRI properties of the Mn-iCOF may open new avenues for designing more biocompatible MRI contrast agents with higher resolutions, particularly in the diagnosis of TNBC.

Amorphous Albumin Gadolinium-Based Nanoparticles for Ultrahigh-Resolution Magnetic Resonance Angiography

“…A remarkably high r 1 of about 76.7 mM –1 s –1 at 3T was recorded for BSA-Gd, which was nearly 16-fold higher than that of the commercial contrast agent Gd-DTPA (4.7 mM –1 S –1 ) and 7-fold more robust than that of BSA-Gdx under the same condition. The significantly enhanced relaxivity of BSA-Gd may be attributed to the following reasons: 1) the binding of gadolinium and macromolecular albumin increases the molecular weight of the entire contrast agent, thereby slowing down the rotational motion of the complex, and 2) the high hydrophilicity of undenatured albumin allows water molecules around BSA-Gd to easily expose to gadolinium oxide for inner-sphere water relaxation. − Figure I presents the kinetics of the MR signal in the blood vessels of rats after the contrast agents were intravenously injected. Under the same dose of the Gd concentration, BSA-Gd reached a much stronger signal and a longer blood circulation time with a t 1/2 of about 40 min in comparison to Gd-DTPA ( t 1/2 = 2 min).…”

Mn-Based MRI Contrast Agents: An Overview

“…For example, Aoki et al [132] developed Mn-MOF-74, where the ligand dihydroxyterephthalate (DHTP) self-assembles with Mn 2+ ions to form a honeycomb-like structure with a diameter of 1.0 nm. They obtained an interesting relaxivity of about 10 s −1 mM −1 at 1.0 T and 23 • C. Zhao et al [133] developed a Mn(II)-chelated ionic covalent organic framework (iCOF) and also obtained an interesting relaxivity (8 s −1 mM −1 at 3.0 T and 25 • C). Natural organic particles can also be used, such as proteins, and this has notably been exploited recently by Colombo et al [134] who loaded Mn ions in H-ferritin, a recombinant variant of human apoferritin consisting of 24 self-assembled heavy-chains subunits.…”

Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy

“…Thus, MnO 2 -poly(I : C)@COF promotes the tumor antigen presentation of dendritic cells, magnifies the infiltration of cytotoxic T cells into tumor tissues, and strengthens tumor cell elimination. Similarly, in 2023, Zhao et al [210] synthesized a T 1 -weighted MRI contrast agent, Mn-iCOF, by embedding Mn 2 + in the porphyrin moiety of a cationic COF. The contrast agent provided a higher signal-to-noise ratio and longer retention time than commercial Gd-based gadoteric acid.…”