Magnetic Mesoporous Silica Nanorods Loaded with Ceria and Functionalized with Fluorophores for Multimodal Imaging

Abstract

Multifunctional magnetic nanocomposites based on mesoporous silica have a wide range of potential applications in catalysis, biomedicine, or sensing. Such particles combine responsiveness to external magnetic fields with other functionalities endowed by the agents loaded inside the pores or conjugated to the particle surface. Different applications might benefit from specific particle morphologies. In the case of biomedical applications, mesoporous silica nanospheres have been extensively studied while nanorods, with a more challenging preparation, have attracted much less attention despite the positive impact on the therapeutic performance shown by seminal studies. Here, we report on a sol–gel synthesis of mesoporous rodlike silica particles of two distinct lengths (1.4 and 0.9 μm) and aspect ratios (4.7 and 2.2) using Pluronic P123 as a structure-directing template and rendering ∼1 g of rods per batch. Iron oxide nanoparticles have been synthesized within the pores yielding maghemite (γ-Fe 2 O 3 ) nanocrystals of elongated shape (∼7 nm × 5 nm) with a [110] preferential orientation along the rod axis and a superparamagnetic character. The performance of the rods as T 2 -weighted MRI contrast agents has also been confirmed. In a subsequent step, the mesoporous silica rods were loaded with a cerium compound and their surface was functionalized with fluorophores (fluorescamine and Cyanine5) emitting at λ = 525 and 730 nm, respectively, thus highlighting the possibility of multiple imaging modalities. The biocompatibility of the rods was evaluated in vitro in a zebrafish ( Danio rerio ) liver cell line (ZFL), with results showing that neither long nor short rods with magnetic particles caused cytotoxicity in ZFL cells for concentrations up to 50 μg/ml. We advocate that such nanocomposites can find applications in medical imaging and therapy, where the influence of shape on performance can be also assessed.

Bioevaluation of magnetic mesoporous silica rods: cytotoxicity, cell uptake and biodistribution in zebrafish and rodents

“…MSR of Santa Barbara Amorphous-15 (SBA-15) type were synthesized using a sol–gel method described in our previous work. 32 Herein, we focus on the safety and biodistribution of rod-like silica particles of two distinct lengths (1.4 and 0.9 μm) and aspect ratios (AR = 4.7 and 2.2), denominated as long rods (LR) and short rods (SR) and with additional specific functionalizations. Namely, those rods were modified by growing superparamagnetic maghemite (γ-Fe 2 O 3 ) nanocrystals within the pores (Fe 2 O 3 @LR, Fe 2 O 3 @SR).…”

“…We thus conclude that sequences of axial planes were more effective in imaging the liver with the Fe 2 O 3 @SR. Furthermore, considering the better relaxivity value for the Fe 2 O 3 @LR, 32 this system should also be investigated in the future now that it is proved that the rats did not show adverse effects under the administration of SR.…”

“…Extensive details on the synthesis and functionalization of the MSR used in this work have been previously reported. 32 Briefly, Pluronic P123 was dissolved in 1.7 M hydrochloric acid solution. After obtaining a homogeneous solution, the temperature was increased to 40 °C and the solution was stirred at 700 rpm.…”

“…Recently, we synthesized MSR with two distinct aspect ratios (∼2 and ∼5). 32 We equipped the MSR with multiple imaging modalities, loading the pores with magnetic nanoparticles and functionalizing their surface with fluorophores of two emission wavelengths. Here, by using magnetic measurements, fluorescence molecular imaging (FMI), and magnetic resonance imaging (MRI), we investigated the toxicity and biodistribution of the MSR in two in vivo preclinical models of different complexity.…”

Key Parameters for the Rational Design, Synthesis, and Functionalization of Biocompatible Mesoporous Silica Nanoparticles

“…The incorporation of magnetic NPs allows for the use of the functionalized MSNs-based nanocarriers as non-invasive MRI agents for the real-time monitoring of the tumor treatment process in living animals [40]. MSNs have also been used in conjunction with both the OI and MRI imaging modalities [172]. OI is a relatively low-cost technology that allows for rapid screening and MRI can offer high resolution, while simultaneously obtaining physiological and anatomical information [43].…”