Evaluation of a novel fluorescent nanobeacon for targeted imaging of Thomsen-Friedenreich associated colorectal cancer

Abstract

The Thomsen–Friedenreich (TF) antigen represents a prognostic biomarker of colorectal carcinoma. Here, using a nanobeacon, the surface of which was fabricated with peanut agglutinin as TF-binding molecules, we demonstrate that the nanobeacon is able to detect TF antigen in frozen and freshly biopsied polyps using fluorescence microscopy. Our results provide important clues about how to detect aberrant colonic tissues in the most timely fashion. Given the versatile application method for this topical nanobeacon, the protocol used in this work is amenable to clinical colonoscopy. Moreover, the prospects of clinical translation of this technology are evident.

Tumor recognition of peanut agglutinin-immobilized fluorescent nanospheres in biopsied human tissues

“…This data strongly supported that the nanobeacon was very specific for detection of colorectal cancer. The current observation was consistent with our previously reported results [23,28]. The difference in intensities of the nanobeacon-emitted fluorescence between both the tissues was presumably due to high expression of the TF antigen in cancer tissues that was recognized by PNA on the nanosphere surface.…”

“…Furthermore, an extremely thin layer of poly(N-vinylacetamide) (PNVA) was fabricated on the outer surface of the nanobeacon to reduce non-specific interaction with the gastrointestinal mucosa as reported previously [23,24,25,26]. We have previously tested and confirmed the sensitivity and specificity of the nanobeacon for detection of colorectal cancer in imaging based on human colorectal cancer cells [24] and orthotopic rodent models [12,26,27] as well as ex vivo optical imaging using freshly biopsied specimens from clinical surgery [28]. The diagnosis of colorectal cancer by the nanobeacon accompanies identification of the cancer location under endoscopic observation.…”

“…Our latest study demonstrated that there was a unique pattern of fluorescence intensities in illuminations in pathological and non-pathological tissues by the nanobeacon; it was utilized as a quantitative algorithm to differentiate normal tissues from cancer ones [28]. That work also indicated that tumors would be distinguished from normal tissues through comparison of the areas with fluorescence intensities that were larger than the predetermined thresholds.…”

“…The optical imaging was performed under experimental protocols established in our latest publication [28]. In general, mouse tissues were treated with the nanobeacon dispersed in PBS (+) at a concentration of 10 mg/mL (0.1 mL) on ice for 2 min.…”

Interactions Between Tumor Biology and Targeted Nanoplatforms for Imaging Applications

“…These NPs showed a high binding affinity to the CRC‐associated Thomsen–Friedenreich (TF) antigen. The designed nano‐beacon could be used for the clinical detection of hidden polyps, early quantitative detection of CRC, and for distinguishing adenomas and adenocarcinomas from normal colonic tissue 171…”