Bifunctional Pyrrolidin-2-one Terminated Manganese Oxide Nanoparticles for Combined Magnetic Resonance and Fluorescence Imaging

Abstract

Multimodal probes are an asset for simplified, improved medical imaging. In particular, fluorescence and magnetic resonance imaging (MRI) are sought-after combined capabilities. Here, we show that pyrrolidin-2-one-capped manganese oxide nanoparticles (MnO pyrr NPs) combine MRI with fluorescence microscopy to function as efficient bifunctional bio-nanoprobes. We employ a one-pot synthesis for ca. 10 nm MnO NPs, wherein manganese­(II) 2,4-pentadionate is thermally decomposed using pyrrolidin-2-one as a solvent and capping ligand. The MnO pyrr NPs are soluble in water without any further postsynthetic modifications. The r 1 relaxivity and r 2 /r 1 ratio indicate that these NPs are potential T 1 MRI contrast agents at clinical (3 T) and ultrahigh (9.4 T) magnetic fields. Serendipitously, the as-prepared NPs are photoluminescent. The unexpected luminescence is ascribed to the modification of the pyrrolidin-2-one during the thermal treatment. MnO pyrr NPs are successfully used to enable fluorescence microscopy of HeLa cells, demonstrating bifunctional imaging capabilities. A low cytotoxic response in two distinct cell types (HeLa, HepG2) supports the suitability of MnO pyrr NPs for biological imaging applications.

Sic Parvis Magna: Manganese-Substituted Tricalcium Phosphate and Its Biophysical Properties

“…As far as the applications of manganese in biomaterials are concerned, the core of its applications has been in cancer nanomedicine, including both diagnostic and therapeutic uses. For example, Mn 2+ , a paramagnetic metal center with five unpaired electrons and a high spin state ( S = 5/2), can be a less toxic substitute for Gd 3+ as the contrast agent in the most clinically preferred, T 1 mode of magnetic resonance imaging (MRI), where the longitudinal relaxation time of water protons is shortened and used to create a signal . With this rationale in mind, ionic manganese has found a way to numerous composite particles as a dopant, including so-called “magnus nanobullets”, where in couple with magnetite working in the T 2 MRI mode, it enabled dual T 1 /T 2 visualization of tissues .…”

“…For example, Mn 2+ , a paramagnetic metal center with five unpaired electrons and a high spin state (S = 5/2), can be a less toxic substitute for Gd 3+ as the contrast agent in the most clinically preferred, T 1 mode of magnetic resonance imaging (MRI), where the longitudinal relaxation time of water protons is shortened and used to create a signal. 20 With this rationale in mind, ionic manganese has found a way to numerous composite particles as a dopant, including so-called "magnus nanobullets", where in couple with magnetite working in the T 2 MRI mode, it enabled dual T 1 /T 2 visualization of tissues. 21 Manganese dioxide particles also have the ability of breaking down H 2 O 2 to O 2 and thus reducing the conditions of hypoxia, which limits the efficacy of an oxygen consumption process that the photodynamic therapy is.…”

AS1411 aptamer-modified theranostic liposomes co-encapsulating manganese oxide nano-contrast agent and paclitaxel for MRI and therapy of cancer

“…Their uses for tumor MRI in vitro and in vivo have been well documented and a few works have been reported on their combination with drugs for the fabrication of theranostic agents. [23][24][25][26][27] For example, Yan et al developed ultrathin gadolinium oxide nanoscrolls to load an anticancer drug, DOX, which could be degraded in the tumor microenvironment for biocompatible MRI and biodegradationenhanced cancer therapy. 28 Cypate-graed gadolinium oxide nanocrystals (Cy-GdNCs) with cancer targeting capacity for trimodal NIRF/PA/MR imaging and pH-responsive photothermal therapy (PTT) were prepared by conjugating cypate with an albumin scaffold of GdNCs through a carbodiimidecatalyzed amide formation.…”

Metal‐Based Nanoparticle Magnetic Resonance Imaging Contrast Agents: Classifications, Issues, and Countermeasures toward their Clinical Translation

“…It is helpful to highlight that the use of block copolymers, [ 108 ] polyglycerol (PG), [ 109 ] PAA, [ 110 ] and other polymers [ 111 ] have been instrumental in attaining biocompatible MONs contrast agents. Dextran, [ 112 ] 2‐pyrrolidinone (pyrr), [ 113 ] sodium citrate, [ 114 ] calcium lignosulfonate (CaLs), [ 115 ] among others, [ 116 ] have not been left out in the exploration of colloidally stable and biocompatible Mn‐based MRI contrast agents.…”