The majority of the clinically approved iron oxide nanoparticles (IO NPs) used as contrast agents for magnetic resonance imaging (MRI) have been withdrawn from the market either due to safety concerns or lack of profits. To address this challenge, liposomes have been used to prepare IO-based T2 contrast agents. We studied the influence of different phospholipids on the relaxivity (r2) values of magneto-liposomes (MLs) containing magnetic NPs in the bilayer, where a strong correlation between the bilayer fluidity and r2 is clearly shown. Embedding 5-nm IO NPs in the lipid bilayer leads to a significant improvement in their relaxivity, where r2 values range from 153 ± 5 s−1 mM−1 for DPPC/cholesterol/DSPE-PEG (96/50/4) up to 673 ± 12 s−1 mM−1 for DOPC/DSPE-PEG (96/4), compared to “free” IO NPs with an r2 value of 16 s−1 mM−1, measured at 9.4 T MRI scanner. In vitro MRI measurements, together with the ICP-MS analysis, revealed MLs as highly selective contrast agents that were preferentially taken up by cancerous T24 cells, which led to an improvement in the contrast and an easier distinction between the healthy and the cancerous cells. A careful selection of the lipid bilayer to prepare MLs could offer efficient MRI contrast agents, even at very low IO NP concentrations.
Relaxivity r2 and thus the contrast efficacy of superparamagnetic nanoparticles (NPs) can be enhanced via either NP’s magnetic properties or coating optimization. Numerous reports can be found about the investigation of the optimal iron oxide nanoparticles (IO NPs) size, shape, crystallinity and composition that yield high saturation magnetization (ms) values and, consequently, high r2 values. Although the use of an appropriate coating can boost up the NPs MRI contrast agent efficiency, this topic has been largely understudied. Therefore, in this review, the factors affording r2 enhancement of spherical magnetic NPs are discussed. Based on the literature, the requirements for an optimal surface coating that may increase r2 values and ensure stability and biocompatibility of NPs are listed. One of the best candidates that fulfil these requirements are liposomes with embedded magnetic NPs, so-called magneto-liposomes. The analysis of the literature elucidated the most appropriate phospholipid compositions for the relaxivity enhancement and for magneto-liposomes in vivo stability. Finally, the future directions in the development of NP-based contrast agents are given. For example, most of the synthetic NPs are recognized and eliminated as a foreign substance by the immune system. To overcome this issue, a design of a biomimetic, cell-membrane-based nanocarrier for contrast agents is proposed. Disguised with cell membranes, NPs or other active components can act as autogenous cells and thus ensure the inherent biocompatibility.
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