Design, Development and Applications of the Silica-Based Contrast Agents in Magnetic Resonance Imaging

Background: The silica-based nanomaterials are playing a major role to harnessing dual or multiple modalities in therapeutic and diagnostic applications. These silica- based materials are separately used as drug carrying substrate or contrast agents for magnetic resonance imaging (MRI). These materials are also used as a combined platform for both drug delivery and MRI contrast agents either as a T1- or T2- or combined T1- and T2- contrast agents for MRI image enhancement. This article presents an overview on the recent development of the ordered mesoporous silica nanoparticles (MSNs) and unordered non-MSNs silica nanoparticles used as MRI contrast agents, and describes their biological evaluations viz. biocompatibility, bio-toxicity, in vitro and in vivo MRI cell imaging, and MRI image enhancement in animals. Methods: Since the development of the silica-based MRI contrast agents started to grow from mid-2000, this review narrowly focusses on the pertinent articles published during the period of 2007 to 2016. Apparently, a large number of research articles reported the dual applications of silica materials both as a drug carrier for controlled release of drug and as a potential contrast agent for MRI image enhancement. This review has taken a structured approach by separately describing the design, development and applications of the MSNs-based materials being ordered in structure and the unordered non-MSNs silica nanoparticles as MRI contrast agents. The MSNs particularly contain Gd-based materials, and the non-MSNs silica nanoparticles contain Gd-, Fe-, and Mn-based materials. The biological evaluations of the MRI contrast agents containing MSNs and non-MSNs silica nanoparticles are also discussed. Results: The review reveals extensive diversities and complexities being involved in developing these materials. It discusses the types of contrast agents being developed; examinations of these materials for possible MRI contrast agents; their functionalities and mechanisms; in situ and in vivo MRI in cells and animals; and, a range of biological evaluations. The development of MRI contrast agents containing the non-MSNs such as, nanocomposites, nanocapsules and core-shell structured materials were associated with designs of enormous complexities where different synthetic techniques were applied such as, functionalising, grafting, tethering, coating and conjugating with polymers. Thus the properties of these developed materials significantly differed from each other. All the developed MRI contrast agents showed good biocompatibility, cell viability, and cell or cancer targeting specificity. Conclusion: Most of the commercially available MRI contrast agents representing the silica- based nanoparticles are found to be T1 contrast agents however, a few T2 contrast agents were also approved for clinical applications. The perspectives, insights and critical reflections on the stability, limitations, relaxivity and toxicity of the MRI contrast agents and, current and future developments of this area of research are presented. Thus, it is anticipated that the future researchers will be benefitted from the discussions presented in this review in understanding of the significance of these materials; a myriad range of complexities being involved in their developments; various implications; and, the future directions towards the development of more sophisticated silica-based MRI contrast agents. Keywords: Animal, MRI, cell, contrast agent, silica nanoparticles, relaxivity, stability, toxicity.