TY - JOUR
T1 - Tumor-Activated Water-Soluble Photosensitizers for Near-Infrared Photodynamic Cancer Therapy
AU - Xiong, Hu
AU - Zhou, Kejin
AU - Yan, Yunfeng
AU - Miller, Jason B.
AU - Siegwart, Daniel J.
PY - 2018/5/16
Y1 - 2018/5/16
N2 - Current photosensitizers (PSs) for photodynamic therapy (PDT) are limited by their low water solubility and tendency to aggregate, low near-infrared (NIR) absorption, and low cancer selectivity. Here, we designed iodinated, water-soluble NIR boron dipyrromethene-based PSs to achieve image-guided and efficient PDT against cancer in vivo that is enhanced by leveraging tumor-specific pH-responsive activation. PEG2k5c-I and PEG2k5c-OMe-I localized to tumors and were activated by acidic pH in the tumor microenvironment to produce 1O2 and fluorescence for efficient PDT and effective cancer detection after intravenous administration. Upon NIR irradiation, these PSs exhibited strong NIR absorption at 660 and 690 nm, stable NIR emission at 692 and 742 nm, and high 1O2 quantum yields of 0.78 and 0.72 in acidic pH. PEG2k5c-I and PEG2k5c-OMe-I killed cancer cells upon irradiation of NIR light and were nontoxic without irradiation. Light-activated PDT treatment of breast cancer tumors in mice resulted in suppression of tumor growth, DNA damage, and necrosis selectively in tumors. This work thus introduces a versatile method to directly synthesize modular pH-responsive water-soluble PSs and provides a versatile strategy for activatable PDT against cancer.
AB - Current photosensitizers (PSs) for photodynamic therapy (PDT) are limited by their low water solubility and tendency to aggregate, low near-infrared (NIR) absorption, and low cancer selectivity. Here, we designed iodinated, water-soluble NIR boron dipyrromethene-based PSs to achieve image-guided and efficient PDT against cancer in vivo that is enhanced by leveraging tumor-specific pH-responsive activation. PEG2k5c-I and PEG2k5c-OMe-I localized to tumors and were activated by acidic pH in the tumor microenvironment to produce 1O2 and fluorescence for efficient PDT and effective cancer detection after intravenous administration. Upon NIR irradiation, these PSs exhibited strong NIR absorption at 660 and 690 nm, stable NIR emission at 692 and 742 nm, and high 1O2 quantum yields of 0.78 and 0.72 in acidic pH. PEG2k5c-I and PEG2k5c-OMe-I killed cancer cells upon irradiation of NIR light and were nontoxic without irradiation. Light-activated PDT treatment of breast cancer tumors in mice resulted in suppression of tumor growth, DNA damage, and necrosis selectively in tumors. This work thus introduces a versatile method to directly synthesize modular pH-responsive water-soluble PSs and provides a versatile strategy for activatable PDT against cancer.
KW - activatable nanoprobes
KW - near-infrared
KW - pH-responsive fluorescence imaging
KW - photodynamic therapy
KW - photosensitizer
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U2 - 10.1021/acsami.8b04710
DO - 10.1021/acsami.8b04710
M3 - Article
C2 - 29697248
AN - SCOPUS:85046537268
SN - 1944-8244
VL - 10
SP - 16335
EP - 16343
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 19
ER -