Rh-I-UEA-1 Polymerized Liposomes Target and Image Adenomatous Polyps in the APC^Min/+ Mouse Using Optical Colonography

Abstract

Mutated adenomatous polyposis coli (APC) genes predispose transformations to neoplasia progressing to colorectal carcinoma (CRC). Early detection facilitates clinical management and therapy. Novel lectin-mediated polymerized targeted liposomes (Rh-I-UEA-1), with polyp specificity and incorporated imaging agents, were fabricated to locate and image adenomatous polyps in APCMin/+ mice. The biomarker α-L-fucose covalently joins liposomal conjugated lectin ulex euroapeus agglutinin (UEA-1), via glycosidic linkage to the polyp mucin layer. Multispectral optical imaging (MSI) corroborated a global perspective of specific binding (Rhodamine B 532 nm emission, 590–620 nm excitation) of targeted Rh-I-UEA-1 polymerized liposomes to polyps with 1.4× fold labeling efficiency. High-resolution co-registered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) reveal spatial correlation of contrast distribution and tissue morphology. Freshly excised APCMin bowels were incubated with targeted liposomes (UEA-1 lectin), control liposomes (no lectin), or Omnipaque and imaged by the three techniques. CT quantitative analyses did not confirm targeted liposomes more strongly bound polyps than nontargeted liposomes or Omnipaque alone. OCT, with anatomical depth capabilities, along with the co-registered FMI, substantiated Rh-I-UEA-1 liposome binding along the mucinous polyp surface. UEA-1 lectin denotes α-L-fucose biomarker carbohydrate expression at the mucin glycoprotein layer; Rh-I-UEA-1 polymerized liposomes target and image adenomatous polyps in APCMin mice.

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“…Rhodamine-labeled liposomes, similar to those used by others in the ex vivo study of UEA1 targeting, were also synthesized and placed in PBS/mucus, for comparison. 24 As shown in Figure 3c, the fluorescence intensities of both FMSN-PEG-UEA1 and Rhodamine-labeled liposomes remained stable for the first 4 hrs of their respective exposures. However, after a little over 24 hrs, the fluorescence intensity of Rhodamine liposomes in mucus dropped to nearly one-half its initial value, reflecting significant compromises of the liposome membrane’s integrity, as shown in Figure 3c.…”

“…The α-L-fucose-binding lectin UEA1, as noted above, has recently been postulated to be a promising marker in the early detection of colorectal carcinomas 23, 24, 40 . In a recent ex vivo study UEA1-labeled fluorescent liposomes, similar to those used in our work for comparison with our FMSNs, demonstrated significant affinity for adenomatous polyps in colon tissues that had been harvested from APC min/+ mice.…”

“…In a recent ex vivo study UEA1-labeled fluorescent liposomes, similar to those used in our work for comparison with our FMSNs, demonstrated significant affinity for adenomatous polyps in colon tissues that had been harvested from APC min/+ mice. 24 In those studies, however, the liposome’s cavity was reserved for the conveyance of other moieties, relegating the incorporation of limited numbers of fluorescent reporters to the liposome’s membrane and thereby constraining the nanoplatform’s brightness and thus detectability. Such membrane localization of fluorophores can also potentially afford environmental mitigation of fluorescence intensity (e.g., O2 quenching), as well as result in decreased structural integrity of the liposome’s membrane.…”

“…And high-resolution co-registered optical coherence tomography, fluorescence molecular imaging, and multispectral optical imaging has revealed that UEA1 labeled liposomes possess significantly greater targeting efficiency than control liposomes. 24, 25 These ex vivo findings suggest that the fucose-binding lectin UEA1 might be useful in the early detection of colorectal carcinomas by in vivo imaging techniques.…”

“…24 Briefly, 4 µmole of DAPC and DMPE were mixed with 0.08 µ mole of Rhodamine B PE in 2 mL chloroform. Lipid film was formed after removing chloroform via rotory evaporation.…”