Shape-dependent cellular behaviors and relaxivity of iron oxide-based T₁MRI contrast agents

Abstract

Recent research efforts about iron oxide nanoparticles has focused on the development of iron oxide-based T contrast agents for magnetic resonance imaging (MRI), such as ultrasmall iron oxide nanospheres (USNPs <4 nm) and ultrathin nanowires (NW, diameter <4 nm). In this paper, we report the cellular uptake behaviors of these two types of ultrasmall scale nanostructures on HepG2 cells. Both these two nanostructures were functionalized with tannic acid and their physical and chemical properties were carefully analyzed before cellular tests. Both USNPs and NWs exhibited strong paramagnetic signals, a property suitable for T MRI contrast agents. The distinct shapes also caused much difference in their cellular uptake behaviors. Specifically, the uptake of USNPs was five times higher than that of NWs after 72 hours incubation. The shape-dependent cellular uptake can potentially lead to different blood circulation times, and subsequently different applications of these two types of ultrasmall nanostructures.

Focused ultrasound blood brain barrier opening mediated delivery of MRI-visible albumin nanoclusters to the rat brain for localized drug delivery with temporal control

“…FUS has gained attention as a tool for focal BBB 24 opening (BBBO) [4][5][6][7][8][9][10], and can penetrate the skull to safely open the BBB at specific 25 locations [5,[11][12][13][14][15][16]. It is an ideal tool for focal drug delivery due to its current use in 26 humans [17,18] and its non-invasive nature [19,20]. However, brain localization of 27 systemically delivered agents requires that they do not readily cross the BBB and 28 systemic delivery of drugs can cause off target side effects.…”

“…We have shown previously 34 that albumin-based nanoclusters (NCs) can be embedded with ultrasmall iron oxide 35 nanoparticles (USNPs) to provide MRI visibility and can encapsulate dye molecules as 36 well as antibodies [25]. Furthermore, NC load remained inside the NC unless digested 37 with trypsin, and in vivo, NCs remained stable for up to 24 hours [25,26]. Here, we 38 investigated whether albumin-based NCs could be delivered to the rat hippocampus via 39 MRI guided transcranial FUS BBBO for localized drug delivery.…”

“…The release of 45 glutamate from NCs in vivo caused local neuronal activation demonstrating that the 46 drug loading capacity of the NCs is sufficient for inducing localized changes in neural 47 activity with temporal control. 48 Materials and Methods 49 Nanocluster formation and FUS-induced drug release 50 NCs were created as described previously [25,26]. Briefly, first tannic acid-coated 51 ultrasmall (¡4 nm) iron oxide nanoparticles were synthesized [26], followed by 52 crosslinking of nanoparticles with bovine serum albumin proteins by the addition of 53 ethanol and glutaraldehyde.…”

“…48 Materials and Methods 49 Nanocluster formation and FUS-induced drug release 50 NCs were created as described previously [25,26]. Briefly, first tannic acid-coated 51 ultrasmall (¡4 nm) iron oxide nanoparticles were synthesized [26], followed by 52 crosslinking of nanoparticles with bovine serum albumin proteins by the addition of 53 ethanol and glutaraldehyde. The overall size of the nanocluster can be tuned by altering 54 the amounts and rates of ethanol addition.…”

“…Additionally, this method can 303 enable the research and use of drugs that do not normally cross the BBB.To make the NCs MRI visible, our collaborator Dr. Yuping Bao has developed 305 ultrasmall iron oxide-based contrast agents. Nanoparticle-based T1 MRI contrast agents 306 have become increasingly attractive markers for drug delivery[46] [47][45] [25,26,48].…”