TY - JOUR
T1 - Hypoxia Induced by Upconversion-Based Photodynamic Therapy
T2 - Towards Highly Effective Synergistic Bioreductive Therapy in Tumors
AU - Liu, Yanyan
AU - Liu, Yong
AU - Bu, Wenbo
AU - Cheng, Chao
AU - Zuo, Changjing
AU - Xiao, Qingfeng
AU - Sun, Yong
AU - Ni, Dalong
AU - Zhang, Chen
AU - Liu, Jianan
AU - Shi, Jianlin
N1 - Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive pro-drugs that can be activated at low-oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica-shelled upconversion nanoparticles (UCNPs) nanostructure capable of co-delivering photosensitizer (PS) molecules and a bioreductive pro-drug (tirapazamine, TPZ) were designed (TPZ-UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC-based (UC-) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC-PDT. Treatment with TPZ-UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC-PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much-enhanced cytotoxicity of TPZ under PDT-induced hypoxia.
AB - Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive pro-drugs that can be activated at low-oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica-shelled upconversion nanoparticles (UCNPs) nanostructure capable of co-delivering photosensitizer (PS) molecules and a bioreductive pro-drug (tirapazamine, TPZ) were designed (TPZ-UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC-based (UC-) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC-PDT. Treatment with TPZ-UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC-PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much-enhanced cytotoxicity of TPZ under PDT-induced hypoxia.
KW - bioreductive pro-drugs
KW - hypoxia
KW - photodynamic therapy
KW - synergetic therapy
KW - upconversion nanoparticles
UR - https://www.scopus.com/pages/publications/84933518850
U2 - 10.1002/anie.201500478
DO - 10.1002/anie.201500478
M3 - 文章
C2 - 26012928
AN - SCOPUS:84933518850
SN - 1433-7851
VL - 54
SP - 8105
EP - 8109
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 28
ER -