Folate Receptor Targeted Bimodal Liposomes for Tumor Magnetic Resonance Imaging

Abstract

Folate-targeted bimodal paramagnetic and fluorescent liposomes were developed and showed enhanced accumulation in a folate receptor expressing tumor model. These bimodal liposomes were composed of both a paramagnetic and a fluorescent lipid, and utilized a PEG-lipid amphiphile for prolonged in vivo circulation. The particles were formulated to ensure a size distribution of approximately 100 nm with a low polydispersity index. IGROV-1 cells were used to induce tumors in nude Balb/c mice, and the folate-targeted liposomes were injected intravenously. Rapid accumulation of the folate-targeted liposomes within the tumor tissue compared to nontargeted liposomes was observed. Furthermore, folate-labeled liposomes showed a 4-fold increase in tumor T(1) signal intensity at just 2 h postinjection with similar results being obtained for the nontargeted liposomes only 24 h postinjection. In addition, the folate-targeted liposomes were injected at half the nontargeted liposome dose, further demonstrating their effectiveness. Histological analysis of sectioned tumor slices revealed distinct fluorescence patterns between the targeted and nontargeted systems, with a more localized and hyperintense fluorescence signal observed from tumor sections post-folate-targeted liposome injections. These results demonstrate the effectiveness of folate targeting for dynamic real-time solid tumor MRI and provide insight into kinetics of targeted and nontargeted nanoparticles to solid tumors.

Folate receptor-targeted fluorescent paramagnetic bimodal liposomes for tumor imaging

“…11 Lipid-based nanoparticles, such as liposomes, micelles, and microemulsions, have been evaluated as carriers of MRI contrast and fluorescent agents for noninvasive imaging. 9,[12][13][14][15][16][17][18][19][20] There are several recent reviews on lipid-based paramagnetic nanoparticles 21,22 and on paramagnetic and fluorescent nanoparticles. 3,10,23,24 Kostarelos and Miller described a modular design for targeted paramagnetic liposomes carrying nucleic acids, termed Gd-ABCD.…”

“…27 Kamaly et al showed that FR-targeted fluorescent paramagnetic bimodal liposomes have increased accumulation in a FR + murine tumor model. 13 In this study, the authors report the synthesis and evaluation of FR-targeting bimodal liposomes for MRI and fluorescent imaging based on the previously reported Gd-ABCD design. 25 Gd-DTPA-BSA was incorporated into the bilayer of the liposomes as a paramagnetic agent, whereas calcein, a fluorescent dye, was encapsulated in the aqueous core of liposomes.…”

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

“…When introducing macromolecular carriers, signal enhancement to MRI is improved by shortening the T 1 relaxation time of water protons. 2,[23][24][25] Liposomes are by now one of the most successful nanomedicines, which have been applied to deliver a wide variety of chemical molecules, genes, CAs, and even nanoparticles. 26 Compared with other delivery systems (such as nanoparticles, micelles, and carbon nanotubes), liposomes show superior biocompatibility, biodegradability, relatively low toxicity, and improved control over size and surface functionality.…”

“…Some studies have shown that by anchoring ligands in liposome bilayers, the affinity and specificity of liposomal systems to specific targets could be enhanced. 24,25,29 Among the target-specific ligands, aptamers have appeared as promising candidates. 3,4,30 Therefore, GBI-10-targeted gadolinium-loaded liposomes (GTLs) were designed and prepared as a MRI CA for the diagnosis of tumor for the first time in this original study.…”

Silica nanoparticle-based dual imaging colloidal hybrids: cancer cell imaging and biodistribution

“…[24][25][26][27][28][29][30] Ligand-decorated silica particles have been widely used as analytical and biosensing tools. [31][32][33][34][35][36][37][38][39][40] Timely multi-functional MR imaging contrast-enhancing nanoparticles have been studied in biomedical applications. [41][42][43][44][45][46][47][48][49][50][51][52] With the above in mind, we designed silica nanoparticles to have a dual imaging mode, ie, (MR) imaging and fluorescent optical imaging.…”