Photoswitchable Micelles for the Control of
Singlet-Oxygen Generation in Photodynamic Therapies
Zhai, Y (Zhai, Yan)[ 1 ] ; Busscher, HJ (Busscher, Henk J.)[ 3,4 ] ; Liu, Y (Liu, Yong)[ 3,4 ] ; Zhang, ZK (Zhang, Zhenkun)[ 1 ] ; van Kooten, TG (van Kooten, Theo G.)[ 3,4 ] ; Su, LZ (Su, Linzhu)[ 1 ] ; Zhang, YM (Zhang, Yumin)[ 5,6 ] ; Liu, JJ (Liu, Jinjian)[ 5,6 ] ; Liu, JF (Liu, Jianfeng)[ 5,6 ] ; An, YL (An, Yingli)[ 1 ] ; Shi, LQ (Shi, Linqi)[ 1,2 ]
BIOMACROMOLECULES,
2018, 19(6): 2023-2033 特刊: SI
DOI: 10.1021/acs.biomac.8b00085
WOS:000435226200025
Abstract
Inadvertent
photosensitizer-activation and singlet-oxygen generation hampers clinical
application of photodynamic therapies of superficial tumors or subcutaneous
infections. Therefore, a reversible photoswitchable system was designed in
micellar nanocarriers using ZnTPP as a photosensitizer and BDTE as a
photoswitch. Singlet-oxygen generation upon irradiation didnot occur in
closed-switch micelles with ZnTPP/BDTE feeding ratios >1:10. Deliberate
switch closure/opening within 65-80 min was possible through thin layers of
porcine tissue in vitro, increasing for thicker layers. Inadvertent opening of
the switch by simulated daylight, took several tens of hours. Creating
deliberate cell damage and prevention of inadvertent damage in vitro and in
mice could be done at lower ZnTPP/BDTE feeding ratios (1:5) in open-switch
micelles and at higher irradiation intensities than inferred from chemical
clues to generate singlet-oxygen. The reduction of inadvertent photosensitizer
activation in micellar nanocarriers, while maintaining the ability to kill
tumor cells and infectious bacteria established here, brings photo dynamic
therapies closer to clinical application.