TY - JOUR
T1 - Phorbiplatin, a Highly Potent Pt(IV) Antitumor Prodrug That Can Be Controllably Activated by Red Light
AU - Wang, Zhigang
AU - Wang, Na
AU - Cheng, Shun-Cheung
AU - Xu, Kai
AU - Deng, Zhiqin
AU - Chen, Shu
AU - Xu, Zoufeng
AU - Xie, Kai
AU - Tse, Man-Kit
AU - Shi, Peng
AU - Hirao, Hajime
AU - Ko, Chi-Chiu
AU - Zhu, Guangyu
PY - 2019/12/12
Y1 - 2019/12/12
N2 - Selective activation of prodrugs within a tumor is particularly attractive because of their low damage to normal tissue. Here, we report the design, photoactivation mechanism, and antitumor activity of a red-light-activatable Pt(IV) prodrug based on oxaliplatin, a first-line clinical antineoplastic. This small-molecule prodrug, designated as phorbiplatin, has controllable activation property: it is shown to be inert in the dark but under short-period irradiation with low intensity of red light (7 mW/cm2), without the need of any external catalyst, phorbiplatin is rapidly reduced to oxaliplatin. The prodrug displays photocytotoxicity that is up to 1,786 times greater than that of oxaliplatin in human carcinoma cells, and it is also significantly active in vivo. The controllable activation property and superior antitumor activity of phorbiplatin may suggest a novel strategy for the design of visible light-activatable platinum prodrugs to reduce the adverse effects and conquer drug resistance of traditional platinum chemotherapy.
AB - Selective activation of prodrugs within a tumor is particularly attractive because of their low damage to normal tissue. Here, we report the design, photoactivation mechanism, and antitumor activity of a red-light-activatable Pt(IV) prodrug based on oxaliplatin, a first-line clinical antineoplastic. This small-molecule prodrug, designated as phorbiplatin, has controllable activation property: it is shown to be inert in the dark but under short-period irradiation with low intensity of red light (7 mW/cm2), without the need of any external catalyst, phorbiplatin is rapidly reduced to oxaliplatin. The prodrug displays photocytotoxicity that is up to 1,786 times greater than that of oxaliplatin in human carcinoma cells, and it is also significantly active in vivo. The controllable activation property and superior antitumor activity of phorbiplatin may suggest a novel strategy for the design of visible light-activatable platinum prodrugs to reduce the adverse effects and conquer drug resistance of traditional platinum chemotherapy.
KW - cisplatin
KW - drug resistance
KW - oxaliplatin
KW - phorbiplatin
KW - photoactivatable drug
KW - photoactivation mechanism
KW - photoreduction
KW - porphyrin
KW - Pt(IV) prodrug
KW - SDG3: Good health and well-being
UR - http://www.scopus.com/inward/record.url?scp=85076059301&partnerID=8YFLogxK
UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85076059301&origin=recordpage
U2 - 10.1016/j.chempr.2019.08.021
DO - 10.1016/j.chempr.2019.08.021
M3 - RGC 21 - Publication in refereed journal
SN - 2451-9308
VL - 5
SP - 3151
EP - 3165
JO - Chem
JF - Chem
IS - 12
ER -
