Abstract
Magnetic resonance imaging (MRI) is one of the most sophisticated diagnostic tools that is routinely used in clinical practice. Contrast agents (CAs) are commonly exploited to afford much clearer images of detectable organs and to reduce the risk of misdiagnosis caused by limited MRI sensitivity. Currently, only a few gadolinium-based CAs are approved for clinical use. Concerns about their toxicity remain, and their administration is approved only under strict controls. Here, we report the synthesis and validation of a manganese-based CA, namely, Mn@HFn-RT. Manganese is an endogenous paramagnetic metal able to produce a positive contrast like gadolinium, but it is thought to result in less toxicity for the human body. Mn ions were efficiently loaded inside the shell of a recombinant H-ferritin (HFn), which is selectively recognized by the majority of human cancer cells through their transferrin receptor 1. Mn@HFn-RT was characterized, showing excellent colloidal stability, superior relaxivity, and a good safety profile. In vitro experiments confirmed the ability of Mn@HFn-RT to efficiently and selectively target breast cancer cells. In vivo, Mn@HFn-RT allowed the direct detection of tumors by positive contrast enhancement in a breast cancer murine model, using very low metal dosages and exhibiting rapid clearance after diagnosis. Hence, Mn@HFn-RT is proposed as a promising CA candidate to be developed for MRI.
Highlights
The early detection of cancer is a huge and important challenge in clinical settings
Designed to detect malignant lesions with strong selectivity and higher sensitivity compared to most Mn- and Gd-based contrast agents (CAs) reported to date
Despite its lower encapsulation efficiency, Mn@HFn-RT was selected for further investigations because, when tested at equal HFn concentrations, it proved to be able to enhance the signal brightness at the same level of the nanocomplex generated at 65 °C (Mn@HFn-HT) without substantially affecting cellular metabolic activity
Summary
The early detection of cancer is a huge and important challenge in clinical settings. The timing of diagnosis is essential for increasing the chance of efficiently treating and eradicating tumor formations.[1] Magnetic resonance imaging (MRI) is a technique that is able to capture the images of inner body regions by exploiting the principle of nuclear magnetic resonance (NMR), which is based on differences in the longitudinal (T1) and transverse (T2) relaxation time of the hydrogen spin of water molecules. To enhance the contrast within different tissues and facilitate the detection of abnormal regions, it is possible to inject contrast agents (CAs), metal-based compounds capable of decreasing the relaxation times of T1 and T2 of the interacting water molecules present in the body. The results are brighter (T1) or darker (T2) weighted images.[2]
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