Toxicity studies of coumarin 6-encapsulated polystyrene nanospheres conjugated with peanut agglutinin and poly(N-vinylacetamide) as a colonoscopic imaging agent in rats

Abstract

We are investigating an imaging agent that detects early-stage primary colorectal cancer on the mucosal surface in real time under colonoscopic observation. The imaging agent, which is named the nanobeacon, is fluorescent nanospheres conjugated with peanut agglutinin and poly(N-vinylacetamide). Its potential use as an imaging tool for colorectal cancer has been thoroughly validated in numerous studies. Here, toxicities of the nanobeacon were assessed in rats. The nanobeacon was prepared according to the synthetic manner which is being established as the Good Manufacturing Practice-guided production. The rat study was performed in accordance with Good Laboratory Practice regulations. No nanobeacon treatment-related toxicity was observed. The no observable adverse effect levels (NOAEL) of the nanobeacon in 7-day consecutive oral administration and single intrarectal administration were estimated to be more than 1000 mg/kg/day and 50 mg/kg/day, respectively. We concluded that the nanobeacon could be developed as a safe diagnostic agent for colonoscopy applications.

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

“…The particle size and zeta potential were measured in neutral solution whose pH corresponded to that of the administration site (the large intestine) of the nanobeacon. The characteristics were almost identical to those described previously [26,27,29,30,31]. Our past study on the stability of the nanobeacon indicated that the characteristics would be constant through the current research [29].…”

“…The characteristics were almost identical to those described previously [26,27,29,30,31]. Our past study on the stability of the nanobeacon indicated that the characteristics would be constant through the current research [29]. All batches were used for mouse studies.…”

“…The nanobeacon was characterized using the procedures described in our previous studies [26,27,29,30]. Briefly, weight-average and number-average molecular weights (Mw and Mn) of PNVA and PMAA were determined by gel permeation chromatography (GPC).…”

“…The rat study in accordance with Good Laboratory Practice regulations has already demonstrated that the nanobeacon can be developed as a safe diagnostic agent for colonoscopy applications [29], although additional toxicity studies such as uptake of the nanobeacon by M cells on Peyer's patches may be required. In order to bring the technology one step closer to clinical trials, the present study was performed with 2 objectives: (i) validation of diagnostic capabilities of the nanobeacon for detection of colorectal cancer and (ii) evaluation for its potential use in the clinic.…”

Light-Responsive, Shape-Switchable Block Copolymer Particles

“…As expected, the BCP particles were initially spherical with PS-outermost layer because of the preferential hydrophobic interactions of PS with alkyl chains of both N-CTAB and C-CTAB (Figure 3b). 48,54,60 The BCP particles were then sequentially irradiated at 420 nm, followed by 254 nm to investigate the resulting shape and morphological changes (Figures 3b−d). Irradiation at 420 nm led to a transformation of particle shape from spheres with onion-like morphology to prolate ellipsoids with stacked lamellar morphology.…”