Toxicity studies of coumarin 6-encapsulated polystyrene nanospheres conjugated with peanut agglutinin and poly(N-vinylacetamide) as a colonoscopic imaging agent in rats.
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 1000mg/kg/day and 50mg/kg/day, respectively. We concluded that the nanobeacon could be developed as a safe diagnostic agent for colonoscopy applications.


BACKGROUND
Colon cancer remains a major cause of death. Early detection can result in early treatment and thus survival. In this article, the authors tested potential systemic toxicity of coumarin 6-encapsulated polystyrene nanospheres conjugated with peanut agglutinin (PNA) and poly(N-vinylacetamide) (PNVA), which had been shown to bind specifically to colonic cancer cells and thus very promising in colonoscopic detection of cancer cells.
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka Japan. Electronic address: sakuma@pharm.setsunan.ac.jp.
Shinji
S
Sakuma
Life Science Materials Laboratory, ADEKA Co., Tokyo, Japan.
Hironori
H
Kumagai
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka Japan.
Moe
M
Shimosato
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka Japan.
Tokio
T
Kitamura
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka Japan.
Kohta
K
Mohri
Life Science Materials Laboratory, ADEKA Co., Tokyo, Japan.
Tetsuya
T
Ikejima
Life Science Materials Laboratory, ADEKA Co., Tokyo, Japan.
Ken-Ichiro
K
Hiwatari
Life Science Materials Laboratory, ADEKA Co., Tokyo, Japan.
Seiji
S
Koike
Life Science Materials Laboratory, ADEKA Co., Tokyo, Japan.
Etsuo
E
Tobita
Institute of Imaging Science, Medical Center, Vanderbilt University, Nashville, TN, USA.
Richard
R
McClure
Institute of Imaging Science, Medical Center, Vanderbilt University, Nashville, TN, USA.
John C
JC
Gore
Institute of Imaging Science, Medical Center, Vanderbilt University, Nashville, TN, USA. Electronic address: wellington.pham@Vanderbilt.Edu.
Wellington
W
Pham
D000081:Acetamides / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D018938:Caco-2 Cells; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D003412:Cricetulus; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D008297:Male; D054118:Nanospheres / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D019887:Peanut Agglutinin / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011137:Polystyrenes / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011145:Polyvinyls / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D012007:Rectum / Q000187:drug effects / Q000473:pathology; D013844:Thiazoles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
D000081:Acetamides; D003374:Coumarins; D005456:Fluorescent Dyes; D019887:Peanut Agglutinin; D011137:Polystyrenes; D011145:Polyvinyls; D013844:Thiazoles; C517282:coumarin 6; C539745:poly(N-vinylacetamide)
Colonoscopic imaging agent; Colorectal cancer; Good Laboratory Practice; Nanosphere; Toxicity study