Surfactant‐Stripped Frozen Pheophytin Micelles for Multimodal Gut Imaging

Abstract

A gut imaging contrast agent would benefit from the following: 1) being edible and generally regarded as safe; 2) transiting stably through the intestine; and 3) activity in multiple modalities. We found that Chlorophyll-a (Chl), a plant pigment that is ubiquitous in human diets, was amenable to formulation in surfactant-stripped induced frozen micelles (ss-InFroMs). However, Chl ss-InFroM stability was limited in gastric conditions in vitro and in vivo. By demetallating Chl to generate pheophytin-a (Pheo), more stable ss-InFroms were obtained which exhibited complete fecal excretion following oral gavage without systemic absorption. Because ss-InFroms could be concentrated to high concentration during the low-temperature stripping of the loose Pluronic surfactant, Pheo ss-InFroMs were used for non-invasive photoacoustic computed tomography of the gut of mice. Unexpectedly, Pheo (but not Chl) ss-InFroms exhibited strong near infrared fluorescence, further enabling non-invasive fluorescence gut imaging. Since Pheo (but not Chl) could be chelated with exogenous metals, Pheo ss-InFroMs could be seamlessly post-labeled with 64Cu for whole body positron emission tomography. Taken together, these results underscore the potential for Pheo, as an edible material, to be re-formulated for higher-order multimodal gut imaging.

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

“…Our findings potentially allow inserting MRI into photomedicine for enhanced visualization. In addition, because a wide variety of free‐base porphyrins possess favorable properties for detection using CEST imaging, conjugation of these probes to water‐soluble polymers, liposomes, or incorporation into micelles should preserve the CEST properties, allowing their use for a wide variety of multimodal diagnostic and theranostic studies.…”

Ingestible Contrast Agents for Gastrointestinal Imaging

“…Furthermore, by using the low‐temperature processing method, pheophytin extracted from the naturally existing dyes in green vegetables can also be encapsulated in pluronic micelles. Pheophytin InFroMs, unlike first‐generation nanonap, can also be used as a contrast agent for fluorescence imaging, in addition to photoacoustic imaging and PET (Figure E–G) . Therefore, InFroMs represent a novel nanoplatform that can be used for multimodal imaging of the intestine .…”

“…Examples of contrastagents Advantages Disadvantages CT bariummeal, [38,41] DCBM, [23] iodinated agent [85] high resolution, high acquisitions peed, low cost exposuret or adiation MRI gadolinium agents, [32] barium sulfate, [88,89] water, [90] natural contrast agents [91,92] minimalr adiation noninvasive, high resolution time consuming PET 18 F, [27,43] 64 Cu [10,93] high sensitivity,h igh specificity,h igh resolution high cost ultrasound microbubbles [94] noninvasive,l ow cost, high safety profile poor sensitivity fluorescence ICG, [95] red chlorophyll, [96] pheophytin [93] high sensitivity,e asy operation susceptible to interference, very poorp enetration depth photoacoustic naphthalocyanines, [10] pheophytin [93] noninvasive,h igh resolution restricted penetration depth Figure 3. Magneticr esonance imagingbyu sing various contrasta gents.…”

“…Pheophytin InFroMs, unlike first-generation nanonap, can also be used as ac ontrast agent for fluorescence imaging, in addition to photoacoustic imaging andP ET (Figure4E-G). [93] Therefore, InFroMs represent an ovel nanoplatformt hat can be used for multimodal imaging of the intestine. [10] Beyond that, other novel imaging strategies are adding new possibilities to the field of theranostics and molecular imaging.…”

Advanced Functional Nanomaterials for Theranostics

“…[51] Micelles can solubilize even extremely hydrophobic materials and in some cases, the excess surfactant can be stripped away to bypass toxicity compared to the simpler approach of dissolving the cargo directly in surfactants. [52, 53] . Furthermore, by choosing the proper micelle unimer, the release rate of cargo can be controlled.…”