Annexin V-CLIO: A Nanoparticle for Detecting Apoptosis by MRI

Organic functionalized magnetic nanoparticles (MNPs) are promising tools for advanced biomedical applications ranging from biosensing and bioseparations to diagnostic and therapeutic techniques such as magnetic resonance imaging, hyperthermia, and controlled drug delivery. The strength point of these tools is the combination of the magnetic properties of the core with the versatility of an organic coating able to impart new and specific functionalities. This chapter summarizes the most relevant achievements in this area, from the material synthesis to the in vitro and in vivo applications in the biomedical field. After a short introduction on the properties and syntheses of the nanomagnetic core, focus is centered on the approaches adopted to functionalize the surface of iron oxide nanoparticles. In particular, the role of different anchoring groups able to bond the coating to the oxide surface is discussed. In addition, the most important chemical routes adopted to conjugate specific functional biomolecules (e.g., optical imaging probes, molecular receptors, targeting molecules, peptides) on the organic-modified surface are reviewed. The multifunctionality of these organic–functionalized Fe₃O₄ nanoparticles is the key to their successful applications and their use is becoming one of the most promising research areas in nanomedicine. In the last paragraphs of this chapter, an overview of the most important applications of MNPs is presented divided into two groups: in vitro applications in which MNPs are designed mainly for laboratory use or on-chip devices and in vivo applications whose main MNPs goal is the injection in a patient for diagnostic, therapeutic, or simultaneous diagnostic/therapeutic purposes (theranostics). Theranostics represents an important milestone in the development of cancer treatments. The ability to track chemotherapy drugs as they move through the body, as well as simultaneously targeting them at cancer cells, will improve the efficacy of the drugs, reduce side effects, and provide valuable data for development of new drugs.

The combination of many nanomaterials and biological components gives the researchers the advantages of both. Recognizing the properties of biocomponents provides selectivity and sensitivity. On the other hand mechanical, catalytical and optical features of nanomaterials make possible the implementation of biomaterials in different fields. Nanomaterials covered with biological materials have great potential in a variety of applications such as bio-detection technologies, targeting and imaging of cancer cells, biofuel cells, food and beverage industry, etc. The use of nanomaterials in medical imaging is increasing rapidly. In this chapter, we provide a brief description of nanomaterials, such as nanoparticles, dendrimers, carbon nanotubes, quantum dots, vesicular systems, and the decoration techniques of nanomaterials with a variety of biological molecules to prepare nanocarrier systems and the use of the obtained nanobiomaterials in targeting and visualization of cancer cells.

The development of magnetic resonance imaging (MRI) has been one of the great medical advances in the twentieth century, enabling the creation of 3D images of the human body with excellent soft tissue contrast and spatial resolution. MRI is noninvasive and does not rely on harmful ionizing radiation. From its early applications in the diagnosis of brain pathology such as stroke, today it is used widely to diagnose and monitor disease processes throughout the body, giving new insights into cancer, heart disease, bowel disorders, and the musculoskeletal system. Advances in scanner hardware, with increasing magnet strength, novel pulse sequences, and improved imaging coils, have greatly enhanced image quality and intrinsic structural contrast. Furthermore, new areas of research into MRI contrast agents and molecular imaging have emerged, which enable pathology to be seen with even greater clarity. In this article, we first explore the history and basic principles of MRI – how the MR signal originates biologically and may be exploited for imaging. We then go on to discuss MR contrast agents, examining the role of the paramagnetic contrast agents in common clinical use. We then move to introduce advanced molecular MRI techniques such as advances in targeted and genetic reporter contrast agents. Finally, we look at MRI’s role in complementing histopathology, discussing MRI for noninvasive imaging of delicate and postmortem samples and the use of MR to image at a microscopic scale.

Given the need for sophisticated in vivo detection techniques to better characterize the cellular and subcellular processes in animals and humans, molecular imaging has become an important discipline. Techniques in molecular imaging have developed from stand alone modalities to multimodality methods. Among these, the combination of positron emission tomography (PET) and computed tomography (CT) is a successful imaging method and has become an important tool in clinical practice. Technological approaches that combine magnetic resonance imaging (MRI) with diffuse optical tomography (DOT), fluorescence tomography (FT) and PET have now been introduced. PET/MRI and the resulting combination of molecular, morphological and functional information will pave the way for a better understanding of physiological and disease mechanisms in preclinical and clinical settings.

Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents that have been developed for magnetic resonance (MR) imaging. These MNPs have traditionally been used for disease imaging via passive targeting, but recent advances have opened the door to cellular-specific targeting, drug delivery, and multi-modal imaging by these nanoparticles. As more elaborate MNPs are envisioned, adherence to proper design criteria (e.g. size, coating, molecular functionalization) becomes even more essential. This review summarizes the design parameters that affect MNP performance in vivo, including the physicochemical properties and nanoparticle surface modifications, such as MNP coating and targeting ligand functionalizations that can enhance MNP management of biological barriers. A careful review of the chemistries used to modify the surfaces of MNPs is also given, with attention paid to optimizing the activity of bound ligands while maintaining favorable physicochemical properties.