TY - JOUR
T1 - Azo-based small molecular hypoxia responsive theranostic for tumor-specific imaging and therapy
AU - Zhou, Ying
AU - Maiti, Mrinmoy
AU - Sharma, Amit
AU - Won, Miae
AU - Yu, Le
AU - Miao, Lan Xi
AU - Shin, Jinwoo
AU - Podder, Arup
AU - Bobba, Kondapa Naidu
AU - Han, Jiyou
AU - Bhuniya, Sankarprasad
AU - Kim, Jong Seung
N1 - Funding Information:
SB thanked to DST-SERB , India for a research grant ( ECR/2015/00035 ). This work was supported by the National Natural Science Foundation of China (Nos. 21462050 and 21672185 ), the Foundation of the Department of Science and Technology of Yunnan Province of China (Nos. 2013HB062 , 2014HB008 , 2016FB020 ), and the Program for Excellent Youth Talents (No. C6176102 ), Yunnan University, and Future Planning in Korea (CRI project no. 2018R1A3B1052702 , J. S. K.)
Publisher Copyright:
© 2018
PY - 2018/10/28
Y1 - 2018/10/28
N2 - We report herein, an azo-derivative (AzP1) of FDA approved antineoplastic drug SN-38 (irinotecan analogue) as a theranostic agent with a potential for both tumor hypoxia-specific activation and therapy. The theranostic AzP1 was found to be stable within a biologically relevant pH scale and was chemically inert towards other competitive biological analytes. However, upon treatment with rat-liver microsomes, AzP1 showed a self-calibrated fluorescence enhancement at λem = 560 nm. The cytotoxicity profile of AzP1 was tested in various cancer lines. Under hypoxic conditions, prodrug AzP1 exhibited activation to release the parent drug (SN-38) and enhanced cytotoxicity in cancer cells with concomitant fluorescence enhancement at 560 nm, which served to monitor both the drug activation and tracing purposes. The therapeutic potential of AzP1 for both tumor-specific activation and suppression of tumor weights was validated in xenograft mouse model. Collectively, the synthetic ease and hypoxia-sensitive activation along with promising therapeutic properties highlight the potential of theranostic AzPI in future cancer treatment programs.
AB - We report herein, an azo-derivative (AzP1) of FDA approved antineoplastic drug SN-38 (irinotecan analogue) as a theranostic agent with a potential for both tumor hypoxia-specific activation and therapy. The theranostic AzP1 was found to be stable within a biologically relevant pH scale and was chemically inert towards other competitive biological analytes. However, upon treatment with rat-liver microsomes, AzP1 showed a self-calibrated fluorescence enhancement at λem = 560 nm. The cytotoxicity profile of AzP1 was tested in various cancer lines. Under hypoxic conditions, prodrug AzP1 exhibited activation to release the parent drug (SN-38) and enhanced cytotoxicity in cancer cells with concomitant fluorescence enhancement at 560 nm, which served to monitor both the drug activation and tracing purposes. The therapeutic potential of AzP1 for both tumor-specific activation and suppression of tumor weights was validated in xenograft mouse model. Collectively, the synthetic ease and hypoxia-sensitive activation along with promising therapeutic properties highlight the potential of theranostic AzPI in future cancer treatment programs.
UR - http://www.scopus.com/inward/record.url?scp=85052658395&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2018.08.036
DO - 10.1016/j.jconrel.2018.08.036
M3 - Article
C2 - 30170068
AN - SCOPUS:85052658395
SN - 0168-3659
VL - 288
SP - 14
EP - 22
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -
